Search results for: anticancer enzyme

Authors: Anas Al-Ali, Mohammed Suleiman, Ayman Hussein

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Sulfur is an important element has many practical applications in present as nanoparticles. Nanosize sulfur particles also have many important applications like in pharmaceuticals, medicine, synthesis of nanocomposites for lithium batteries, modification of carbon nanotubes. Different methods were used for nano-sized particle synthesis; among those, chemical precipitation, electrochemical method, micro-emulsion technique, composing of oil, surfactant, co-surfactant, aqueous phases with the specific compositions and ultrasonic treatment of sulfur-cystine solution. In this work, sulfur nanoparticles (S NPs) were prepared by a quick precipitation method with and without using a surfactant to stabilize the formed S NPs. The synthesized S NPs were characterized by XRD, SEM, and TEM in order to confirm their sizes and structures. Application of nanotechnology is suggested for diagnosis and treatment of cancer. The anticancer activity of the prepared S NPs has been tested on various types of cancer cell clones including leukemia, kidney and colon cancers.

Keywords: sulfur nanoparticles (S-NPs), TEM, SEM, anti cancer activity, XRD

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Authors: Lintle Mohase, Ninikoe Lebusa, Mpho Stephen Mafa

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Wheat is an economically important cereal crop. However, the changing climatic conditions that intensify drought in production areas, and additional pest infestation, such as the Russian wheat aphid (RWA, Diuraphis noxia), severely hamper its production. Drought and pest management require an additional water supply through irrigation and applying inorganic nutrients (including silicon) as alternative strategies to mitigate the stress effects. Therefore, other approaches are needed to enhance wheat productivity during drought stress and aphid abundance. Two wheat cultivars were raised under greenhouse conditions, exposed to drought stress, and treated with silicon before infestation with the South African RWA biotype 2 (RWASA2). The morphological evaluations showed that severe drought or a combination of drought and infestation significantly reduced the plant height of wheat cultivars. Silicon treatment did not alleviate the growth reduction. The biochemical responses were measured using spectrophotometric assays with specific substrates. An evaluation of the enzyme activities associated with oxidative stress and defence responses indicated that drought stress increased NADPH oxidase activity, while silicon treatment significantly reduced it in drought-stressed and infested plants. At 48 and 72 hours sampling periods, a combination of silicon, drought and infestation treatment significantly increased peroxidase activity compared to drought and infestation treatment. The treatment also increased β-1,3-glucanase activity 72 hours after infestation. In addition, silicon and drought treatment increased glucose but reduced sucrose accumulation. Furthermore, silicon, drought, and infestation treatment combinations reduced the sucrose content. Finally, silicon significantly increased the trehalose content under severe drought and infestation, evident at 48 and 72-hour sampling periods. Our findings shed light on silicon’s ability to induce protective biochemical responses during drought and aphid infestation.

Keywords: drought, enzyme activity, silicon, soluble sugars, Russian wheat aphid, wheat

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Authors: Elisangela Sobreira, Denise Teixeira

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Visceral leishmaniasis is a public health problem in Brazil, it is the main reservoir dog. In the period 2012-2016 78 diagnoses were performed in dogs suspected. Blood samples were collected from the cephalic vein obtaining serum used for the indirect immunofluorescence test and enzyme-linked immunosorbent assay, while it collected a drop of blood for the rapid chromatographic immunoassay. Obtained in 32 dogs positive. The test is important for the control of this disease and is used routinely in the Zoonoses Control Center.

Keywords: Brazil, dogs, Leismaniasis, Zoonoses center

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Authors: Hossein Mostafavi

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A diversity of biological activities and pharmaceutical uses have been attributed to gallic acid derivatives such as antibacterial, anticancer, anti inflammatory. A series of gallic acid derivatives were synthesized, and their structure was confirmed by FT-IR, HNMR, CNMR, elemental analysis. In vitro biological activity of compounds was determined against Proteus vulgaris ATCC 7829, Escherichia coli ATCC 25922, as (Gram-negative) bacteria and bacillus cereus ATCC 11778, Staphylococus aureus ATCC 6538 as (Gram-positive) bacteria. Antibacterial susceptibility tests were done by use of the paper disc diffusion method on Mueller Hinton agar (Merck). Chloramiphenicol, Penicilline, Streptomycin and Tetracycline were standard reference antibiotics. The zone of inhibition against bacteria was measured after 24 hours at 37 °C. Compounds 3, 4, 5 were the main antibacterial compounds against Gram-negative bacteria but not Gram-positive.

Keywords: gallic acid derivatives, antibacterial, antibiotics, inhibition

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Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson

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Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.

Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia

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Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Po-Chin Liang, Yung-Chu Chen, Chi-Feng Chiang, Yun-Ping Lin, Wen-Yuan Hsieh, Win-Li Lin

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The aim of this study was to develop super paramagnetic iron oxide (SPIO) nano-particles comprised of a magnetic Fe3O4 core and a shell of aqueous stable self-doped polyethylene glycol (PEG) with a high loading of doxorubicin (SPIO-PEG-D) for tumor theranostics. The in-vivo MRI study showed that there was a stronger T2-weighted signal enhancement for the group under a magnetic field, and hence it indicated that this group had a better accumulation of SPIO-PEG than the group without a magnetic field. In the anticancer evaluation of SPIO-PEG-D, the group with a magnetic field displayed a significantly smaller tumor size than the group without. The overall results show that SPIO-PEG-D nanoparticles have the potential for the application of MRI/monitoring chemotherapy and the therapy can be locally enhanced by applying an external magnetic field.

Keywords: super paramagnetic iron oxide nano particles, doxorubicin, chemotherapy, MRI, magnetic fields

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Authors: Amina Aloui, Jalila Ben Salah-Abbès, Abdellah Zinedine, Amar Riba, Noel Durand, Catherine Brabet, Didier Montet, Samir Abbès

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Mycotoxin contamination of food and feed-isa globaconcern, both economically and for public health. Aflatoxin M1 (AFM1) is the principal hydroxylated metabolite of aflatoxin B1. It is frequently found in milk and other dairy products. It is responsible for the development of hepatocellular carcinoma and immunotoxic in humans and animals. The reduction of its bioavailabilitybecomesa great demand in order to protect human and animal health. The use of probiotic bacteria and clay are demonstrated to be able to bind AFM1 in vitro. This study aimed to investigate, in vivo, the activity of two-component mixture: L. rhamnosusGAF06 (LR) and bentonite for reducing the oxidative stress and the histological alterationsinduced by AFM1 in the liver andkidneys. For the experiment, male mice were divided into 7 groups (6 mice/group) and treated, orally, by AFM1, alone or in combination with LR and/or bentonite, for 10 days as follows: group 1 control, group 2 treated with LR alone (2.108 CFU/ml), group 3 treated with bentonite alone (1g/kg), group 4 treated with AFM1 alone (100μg/kg), group 5 co-treated with LR+AFM1, group 6 co-treated with bentonite+AFM1, group 7 co-treated with bentonite+LR+AFM1. At the end of the treatment, the mice were sacrificed, and the livers and kidneys were collected for histological assays. Intracellular antioxidant activities and lipid peroxidation were also studied. The results showed that AFM1causeddamage in liver and kidney tissues, being evidence of hepatotoxicity and nephrotoxicity marked by necrotic cells. It increased the MDA level and decreased the antioxidant enzyme activities (SOD) in both organs. In contrast, the co-treatment with AFM1 plus LR and/or bentonitesignificantly improved the hepatic and renal tissues, regulated kidney, and liver antioxidant enzyme activities. This improvement was more remarkable with the administration of LR-bentonite mixture with AFM1.LR and bentonite alone showed to be safe during the treatment. This mixture can be a promising candidate for future applications in biotechnological processes that aimed to detoxify AFM1in food and feed.

Keywords: aflatoxin M1, bentonite, L. rhamnosus GAF06, oxidative stress, prevention

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Authors: Vandana Mohan, Ashwani Koul

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Aim: To evaluate the potential of Aqueous Tinospora cordifolia stem extract (Aq.Tc) and Arabinogalactan (AG) on pulmonary carcinogenesis and associated tumor markers. Background: Lung cancer is one of the most frequent malignancy with high mortality rate due to limitation of early detection resulting in low cure rates. Current research effort focuses on identifying some blood-based biomarkers like CEA, ctDNA and LDH which may have potential to detect cancer at an early stage, evaluation of therapeutic response and its recurrence. Medicinal plants and their active components have been widely investigated for their anticancer potentials. Aqueous preparation of T. Cordifolia extract is enriched in the polysaccharide fraction i.e., AG when compared with other types of extract. Moreover, reports are available of polysaccharide fraction of T. Cordifolia in in vitro lung cancer models which showed profound anti-metastatic activity against these cell lines. However, not much has been explored about its effect in in vivo lung cancer models and the underlying mechanism involved. Experimental Design: Mice were randomly segregated into six groups. Group I animals served as control. Group II animals were administered with Aq. Tc extract (200 mg/kg b.w.) p.o.on the alternate days. Group III animals were fed with AG (7.5 mg/kg b.w.) p.o. on the alternate days (thrice a week). Group IV animals were installed with Benzo(a)pyrene (50 mg/kg b.w.), i.p. twice within an interval of two weeks. Group V animals received Aq. Tc extract as in group II along with it B(a)P was installed after two weeks of Aq. Tc administration following the same protocol as for group IV. Group VI animals received AG as in group III along with it B(a)P was installed after two weeks of AG administration. Results: Administration of B(a)P to mice resulted in increased tumor incidence, multiplicity and pulmonary somatic index with concomitant increase in serum/plasma markers like CEA, ctDNA, LDH and TNF-α.Aq.Tc and AG supplementation significantly attenuated these alterations at different stages of tumorigenesis thereby showing potent anti-cancer effect in lung cancer. A pronounced decrease in serum/plasma markers were observed in animals treated with Aq.Tc as compared to those fed with AG. Also, extensive hyperproliferation of alveolar epithelium was prominent in B(a)P induced lung tumors. However, treatment of Aq.Tc and AG to lung tumor bearing mice exhibited reduced alveolar damage evident from decreased number of hyperchromatic irregular nuclei. A direct correlation between the concentration of tumor markers and the intensity of lung cancer was observed in animals bearing cancer co-treated with Aq.Tc and AG. Conclusion: These findings substantiate the chemopreventive potential of Aq.Tc and AG against lung tumorigenesis. Interestingly, Aq.Tc was found to be more effective in modulating the cancer as reflected by various observations which may be attributed to the synergism offered by various components of Aq.Tc. Further studies are in progress to understand the underlined mechanism in inhibiting lung tumorigenesis by Aq.Tc and AG.

Keywords: Arabinogalactan, Benzo(a)pyrene B(a)P, carcinoembryonic antigen (CEA), circulating tumor DNA (ctDNA), lactate dehydrogenase (LDH), Tinospora cordifolia

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Authors: Mahdokht Sadeghvishkaei, Azizah Abdul-Hamid, Amin Ismail, Nazamid Saari

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Hypertension is a common and serious chronic health problem and known as the most important risk factor for development of many diseases such as stroke. Since angiotensin I-converting enzyme (ACE) is the key enzyme involved in blood pressure, one of the well accepted mechanisms to control hypertension is through ACE inhibition. The ACE inhibitory effect of Actinopyga lecanora (stone fish) proteolysate in vitro had been reported. Hence, this study aimed to evaluate the ACE inhibitory potential of Actinopyga lecanora proteolysate in vivo in normotensive rats. Therefore the ACE inhibitory capability of the proteolysate to prevent increasing systolic blood pressure, after inducing hypertension by angiotensin I was examined. The pre-fed rats with the proteolysates at various doses (200, 400, 800 mg/kg body weight) revealed the significant (p ≤ 0.05) suppression effect compared with control groups. Furthermore, different doses of the proteolysate (200, 400, 800 mg/kg body weight) were examined to find its optimum effective dose. Results depicted that 800 mg proteolysate/kg body weight significantly reduced systolic blood pressure without negative effect on normal blood pressure (p ≤ 0.05). Furthermore, Sub-acute toxicity study based on OECD guideline demonstrated the safety of the proteolysate in vivo. The present study indicated that the proteolysate at a dose of 1000 mg/kg daily for 14 days did not cause toxicity signs such as death, changes in activity, or piloerection. Since there are no significant differences between treated groups and control groups, hematological and biochemical analysis confirmed safety of the proteolysate (p > 0.05). In addition, there were no significant differences between organs weights of the treated groups and the control groups. Morphologically, neither histopathological changes, nor gross abnormalities were observed. However, the proteolysate caused significant decrease in body weight in relation to the control groups (p ≤ 0.05) probably due to appetite stimulation by the proteolysate, leading to decreased food consumption in sub-acute group. It is concluded that the proteolysate generated from Actinopyga lecanora possess a significant anti-hypertensive effect and would be potentially used as natural alternative of ACE inhibitors.

Keywords: ACE inhibition, Actinopyga lecanora, anti-hypertensive activity, bioactive peptides, normotensive rats

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Authors: Salman Akrokayan

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Synthetic cDNA (ScDNA) of granulocyte colony-stimulating factor (G-CSF) was constructed using a DNA synthesizer with the aim to increase its expression level. 5' end of the ScDNA of G-CSF coding region was modified by decreasing the GC content without altering the predicted amino acids sequence. The identity of the resulting protein from ScDNA was confirmed by the highly specific enzyme-linked immunosorbent assay. In conclusion, a synthetic G-CSF cDNA in combination with the recombinant DNA protocol offers a rapid and reliable strategy for synthesizing the target protein. However, the commercial utilization of this methodology requires rigorous validation and quality control.

Keywords: synthetic cDNA, recombinant G-CSF, cloning, gene expression

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Authors: Sumayah Mohammed Asiri A., Aviva Levina B., Elizabeth New C., Peter Lay D.

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Pt compounds have been among the most successful anticancer drugs in the last 40 years, but the development of resistance to them is an increasing problem. Cellular homeostasis of an essential metal, Cu, is known to be involved in Pt resistance, but mechanisms of this process are poorly understood. We used a novel ratiometric Cu(I)-sensitive fluorescent probeInCCu1 dye to detect Cu(I) in the mitochondria. Total Cu and labile Cu pool measured using AAS and InCCu1 dye in A2780 cells and their corresponding resistant cells A2780-cis.R cells treated with Cu and cisplatin. The main difference between both cell lines in the presence and absence of Cu(II) is that resistant cells have lower total Cu content but higher labile Cu levels than cisplatin-sensitive cells. This means that resistant cells can metabolize and export excess Cu more efficiently. Furthermore, InCCu1 has emerged not only as an indicator of labile cellular Cu levels in the mitochondria but as a potentially versatile multi-organelle probe.

Keywords: AAS and ICPMS, A2780 and its resistant cells, ratiometric fluorescent sensors, inCCu1, and total and labile Cu

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: Navpreet Kaur, Himkusha Thakur, Nirmal Prabhakar

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The most controversial issue in crop production is the use of Organophosphate insecticides. This is evident in many reports that Organophosphate (OP) insecticides, among the broad range of pesticides are mainly involved in acute and chronic poisoning cases. OPs detection is of crucial importance for health protection, food and environmental safety. In our study, a nanocomposite of poly (3,4 ethylenedioxythiophene) (PEDOT) and multi-walled carbon nanotubes (MWCNTs) has been deposited electrochemically onto the surface of fluorine doped tin oxide sheets (FTO) for the analysis of malathion OP. The -COOH functionalization of MWCNTs has been done for the covalent binding with amino groups of AChE enzyme. The use of PEDOT-MWCNT films exhibited an excellent conductivity, enables fast transfer kinetics and provided a favourable biocompatible microenvironment for AChE, for the significant malathion OP detection. The prepared biosensors were characterized by Fourier transform infrared spectrometry (FTIR), Field emission-scanning electron microscopy (FE-SEM) and electrochemical studies. Various optimization studies were done for different parameters including pH (7.5), AChE concentration (50 mU), substrate concentration (0.3 mM) and inhibition time (10 min). Substrate kinetics has been performed and studied for the determination of Michaelis Menten constant. The detection limit for malathion OP was calculated to be 1 fM within the linear range 1 fM to 1 µM. The activity of inhibited AChE enzyme was restored to 98% of its original value by 2-pyridine aldoxime methiodide (2-PAM) (5 mM) treatment for 11 min. The oxime 2-PAM is able to remove malathion from the active site of AChE by means of trans-esterification reaction. The storage stability and reusability of the prepared biosensor is observed to be 30 days and seven times, respectively. The application of the developed biosensor has also been evaluated for spiked lettuce sample. Recoveries of malathion from the spiked lettuce sample ranged between 96-98%. The low detection limit obtained by the developed biosensor made them reliable, sensitive and a low cost process.

Keywords: PEDOT-MWCNT, malathion, organophosphates, acetylcholinesterase, biosensor, oxime (2-PAM)

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Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Through analysis of a published micro-array-based high-throughput assessment, we discovered that miR-1275 was markedly down-regulated in nasopharyngeal carcinoma (NPC) tissues. However, little is known about its effect and mechanism involved in NPC development and progression. In this study, we investigated the role of miR-1275 on the development of NPC. The results indicated that miR-1275 was significantly down-regulated in primary NPC tissues, and very low levels were found in NPC cell lines. Ectopic expression of miR-1275 in NPC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of HOXB5. In addition, miR-1275 suppresses G1/S transition through inhibition of HOXB5. Further, oncogene HOXB5 was revealed to be a putative target of miR-1275, which was inversely correlated with miR-1275 expression in NPC. Collectively, our study demonstrates that as a tumor suppressor, miR-1275 played a pivotal role on NPC through inhibiting cell proliferation, and suppressing G1/S transition by targeting oncogenic HOXB5.

Keywords: microRNA-1275 (miR-1275), HOXB5, nasopharyngeal carcinoma, proliferation

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Authors: Abdul-Dahiru El-Yuguda, Saka Saheed Baba, Tawa Monilade Adisa, Mustapha Bala Abubakar

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Background: Chikungunya (CHIK) virus, a previously anecdotally described arbovirus, is now assuming a worldwide public health burden. The CHIK virus infection is characterized by potentially life threatening and debilitating arthritis in addition to the high fever, arthralgia, myalgia, headache and rash. Method: Three hundred and seventy (370) serum samples were collected from outpatients with febrile illness attending University of Maiduguri Teaching Hospital, Nigeria, and was used to detect for Chikungunya (CHIK) virus IgG and IgM antibodies using the Enzyme Linked Immunosorbent Assays (ELISAs). Result: Out of the 370 sera tested, 39 (10.5%) were positive for presence of CHIK virus antibodies. A total of 24 (6.5%) tested positive for CHIK virus IgM only while none (0.0%) was positive for presence of CHIK virus IgG only and 15 (4.1%) of the serum samples were positive for both IgG and IgM antibodies. A significant difference (p<0.0001) was observed in the distribution of CHIK virus antibodies in relation to gender. The males had prevalence of 8.5% IgM antibodies as against 4.6% observed in females. On the other hand 4.6% of the females were positive for concurrent CHIK virus IgG and IgM antibodies when compared to a prevalence of 3.4% observed in males. Only the age groups ≤ 60 years and the undisclosed age group were positive for presence of CHIK virus IgG and/or IgM antibodies. No significant difference (p>0.05) was observed in the seasonal prevalence of CHIK virus antibodies among the study subjects Analysis of the prevalence of CHIK virus antibodies in relation to clinical presentation (as observed by Clinicians) of the patients revealed that headache and fever were the most frequently encountered ailments. Conclusion: The CHIK virus IgM and concurrent IgM and IgG antibody prevalence rates of 6.5% and 4.1% observed in this study indicates a current infection and the lack of IgG antibody alone observed shows that the infection is not endemic but sporadic. Recommendation: Further studies should be carried to establish the seasonal prevalence of CHIK virus infection vis-à-vis vector dynamics in the study area. A comprehensive study need to be carried out on the molecular characterization of the CHIK virus circulating in Nigeria with a view to developing CHIK virus vaccine.

Keywords: Chikungunya virus, IgM and IgG antibodies, febrile patients, enzyme linked immunosorbent assay

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Authors: Deepak Kumar Mittal, Alok Kumar Jena, Deepmala Joshi

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The present study was carried out to observe the hepatoprotective effect and antioxidant activity of the aqueous extract of the roots of Polygonum bistorta (PB) (200 mg/kg) and Zingiber roseum (ZR) (250 mg/kg) in rats treated with carbon tetrachloride (0.15 ml/kg, i.p.). Extract of PB and ZR at the tested doses restored the levels of liver homogenate enzymes, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymes, significantly. The activities of MTT assay significantly recovered the damage and supported the biochemical observations. This study suggests that Zingiber roseum has a higher protective effect on liver, compared to Polygonum bistorta, against carbon tetrachloride-induced hepatotoxicity and possesses antioxidant activities. Also, extracts exhibited moderate anticancer activity towards cell viability at higher concentration.

Keywords: Polygonum bistorta, Zingiber roseum, hepatoprotective effect, carbon tetrachloride, anti-cancerous

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Mohamed M. Ibrahim, Gaber A. M. Mersal, Salih Al-Juaid, Samir A. El-Shazly

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A series of mixed ligand complexes, viz., [Cu(BPy)(Gly)X]Y {X = Cl (1), Y = 0; X = 0, Y = ClO4- (2); X = H2O, Y = NO3- (3); X = H2O, Y = CH3COO- (4); and [Cu(BPy)(Gly)-(H2O)]2(SO4) (5) have been synthesized. Their structures and properties were characterized by elemental analysis, thermal analaysis, IR, UV–vis, and ESR spectroscopy, as well as electrochemical measurements including cyclic voltammetry, electrical molar conductivity, and magnetic moment measurements. Complexes 1 and 2 formed slightly distorted square-pyramidal coordination geometries of CuN3OCl and CuN3O2, respectively in which the N,O-donor glycine and N,N-donor bipyridyl bind at the basal plane with chloride ion or water as the axial ligand. Complex 3 shows square planar CuN3O coordination geometry, which exhibits chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The superoxide dismutase and catalase-like activities of all complexes were tested and were found to be promising candidates as durable electron-transfer catalyst being close to the efficiency of the mimicking enzymes displaying either catalase or tyrosinase activity to serve for complete reactive oxygen species (ROS) detoxification, both with respect to superoxide radicals and related peroxides. The DNA binding interaction with super coiled pGEM-T plasmid DNA was investigated by using spectral (absorption and emission) titration and electrochemical techniques. The results revealed that DNA intercalate with complexes 1 and 2 through the groove binding mode. The calculated intrinsic binding constant (Kb) of 1 and 2 were 4.71 and 2.429 × 105 M−1, respectively. Gel electrophoresis study reveals the fact that both complexes cleave super coiled pGEM-T plasmid DNA to nicked and linear forms in the absence of any additives. On the other hand, the interaction of both complexes with DNA, the quasi-reversible CuII/CuI redox couple slightly improves its reversibility with considerable decrease in current intensity. All the experimental results indicate that the bipyridyl mixed copper(II) complex (1) intercalate more effectively into the DNA base pairs.

Keywords: enzyme mimics, mixed ligand complexes, X-ray structures, antioxidant, DNA-binding, DNA cleavage

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Authors: Zakir Hossain, Arzu Pervin, Halima Jahan, Rabeya Akter, Abdel Omri

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Replacement of fish meal with soybean meal is an effective way to relieve the pressure on fish meal as the supply of this feed ingredient is dwindling and certainly is not sustainable in long term at present levels in commercial feeds. This study was designed to determine the effect of fishmeal (FM) replacement with soybean meal (SBM) in diet on growth, digestive enzyme activity, antioxidation and gut histomorphology of tilapia (Oreochromis niloticus). Five diets were formulated where SBM0 contained 100% FM, FM substituted with graded levels of a mix of SBM to replace 25% (SBM25), 50% (SBM50), 75% (SBM75) and 100% (SBM100) of FM. Juvenile tilapia having weight and length of 6.60±0.13 g and 5.42±0.17 cm were randomly divided into five treatment groups having 40 individual each group and fed to visual satiation for 90 days. Diet with SBM was increased significant in body weight gain and specific growth rate in fish compared to the fish fed with SBM100. Fish having the similar weight (74.34±5.41 g) fed the diets SBM50, SBM75 and SBM100 containing higher level of SBM showed significantly longer intestine compared to SBM0. Villus height of stomach and intestine were significantly greater in the fish fed with the diets SBM0, SBM25 and SBM50 compared to SBM100. Muscular thickness was inversely changed with the increasing villus height. Protease activity was increased significantly in stomach, anterior and posterior intestine of fish fed with SBM0 and SBM25 compared to SBM100. In anterior and posterior segment of intestine, significantly higher lipase activity was observed in fish fed with the diets SBM0 and SBM25 compared to diet SBM100. In stomach, amylase activity was also significantly greater in SBM0 compared to SBM100. The antioxidant enzymes including catalase and superoxide dismutase of liver were significantly (P < 0.05) higher in the O. niloticus fed SBM100 compared to the ones fed SBM0. These results suggest that the replacement of FM upto 75% with SBM could be possible considering the growth performances, gut health and activities digestive enzymes and antioxidant enzymes in O. niloticus.

Keywords: soybean meal, fish meal, digestive enzymes, anti-oxidant enzymes

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Authors: G. Amariei, K. Boltes, R. Rosal, P. Leton

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Wastewater treatment plants (WWTPs) are supposed to hold an important place in the reduction of emerging contaminants, but provide an environment that has potential for the development and/or spread of adaptation, as bacteria are continuously mixed with contaminants at sub-inhibitory concentrations. Reviewing the literature, there are little data available regarding the use of adapted bacteria forming activated sludge community for toxicity assessment, and only individual validations have been performed. Therefore, the aim of this work was to study the toxicity of Triclosan (TCS) and Ibuprofen (IBU), individually and in binary combination, on adapted activated sludge (AS). For this purpose a battery of biomarkers were assessed, involving oxidative stress and cytotoxicity responses: glutation-S-transferase (GST), catalase (CAT) and viable cells with FDA. In addition, we compared the toxic effects on adapted bacteria with unadapted bacteria, from a previous research. Adapted AS comes from three continuous-flow AS laboratory systems; two systems received IBU and TCS, individually; while the other received the binary combination, for 14 days. After adaptation, each bacterial culture condition was exposure to IBU, TCS and the combination, at 12 h. The concentration of IBU and TCS ranged 0.5-4mg/L and 0.012-0.1 mg/L, respectively. Batch toxicity experiments were performed using Oxygraph system (Hansatech), for determining the activity of CAT enzyme based on the quantification of oxygen production rate. Fluorimetric technique was applied as well, using a Fluoroskan Ascent Fl (Thermo) for determining the activity of GST enzyme, using monochlorobimane-GSH as substrate, and to the estimation of viable cell of the sludge, by fluorescence staining using Fluorescein Diacetate (FDA). For IBU adapted sludge, CAT activity it was increased at low concentration of IBU, TCS and mixture. However, increasing the concentration the behavior was different: while IBU tends to stabilize the CAT activity, TCS and the mixture decreased this one. GST activity was significantly increased by TCS and mixture. For IBU, no variations it was observed. For TCS adapted sludge, no significant variations on CAT activity it was observed. GST activity it was significant decreased for all contaminants. For mixture adapted sludge the behaviour of CAT activity it was similar to IBU adapted sludge. GST activity it was decreased at all concentration of IBU. While the presence of TCS and mixture, respectively, increased the GST activity. These findings were consistent with the viability cells evaluation, which clearly showed a variation of sludge viability. Our results suggest that, compared with unadapted bacteria, the adapted bacteria conditions plays a relevant role in the toxicity behaviour towards activated sludge communities.

Keywords: adapted sludge community, mixture, PPCPs, toxicity

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Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Morteza Keshavarz

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In this work, using density functional theory (DFT) thermodynamic stability and quantum molecular descriptors of cyclophoshphamide (an anticancer drug)-functionalized zigzag (8,0) CNT, armchair (4,4) CNT and nanocone complexes in water, for two attachment namely the sidewall and tip, is considered. Calculation of the total electronic energy (Et) and binding energy (Eb) of all complexes indicates that the most thermodynamic stability belongs to the sidewall-attachment of cyclophosphamide into functional nanocone. On the other hand, results from chemical hardness show that drug-functionalized zigzag (8,0) and armchair (4,4) complexes in the tip-attachment configuration possess the smallest and greatest chemical hardness, respectively. By computing the solvation energy, it is found that the solution of the drug and all complexes are spontaneous in water. Furthermore, chirality, type of nanovector (nanotube or nanocone), or attachment configuration have no effects on solvation energy of complexes.

Keywords: carbon nanotube, drug delivery, cyclophosphamide drug, density functional theory (DFT)

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Authors: S. N. Harun, H. Ahmad

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A series of ruthenium(II) complexes, including two novel compounds [Ru(dppz)2(L)]2+ where dppz = dipyrido-[3,2-a:2’,3’-c]phenazine, and L = 2-phenylimidazo[4,5-f][1,10]phenanthroline (PIP) or 2-(4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline (p-HPIP) have been synthesized and characterized. The previously reported complexes [Ru(bpy)2L]2+ and [Ru(phen)2L]2+ were also prepared. All complexes were characterized by elemental analysis, 1H-NMR spectroscopy, ESI-Mass spectroscopy and FT-IR spectroscopy. The photophysical properties were analyzed by UV-Visible spectroscopy and fluorescence spectroscopy. [Ru(dppz)2(PIP)]2+ and [Ru(dppz)2(p-HPIP)]2+ displayed ‘molecular light-switch’ effect as they have high emission in acetonitrile but no emission in water. The cytotoxicity of all complexes against cancer cell lines Hela and MCF-7 were investigated through standard MTT assay. [Ru(dppz)2(PIP)]2+ showed moderate toxicity on both MCF-7 and Hela with IC50 of 37.64 µM and 28.02 µM, respectively. Interestingly, [Ru(dppz)2(p-HPIP)]2+ exhibited remarkable cytotoxicity results with IC50 of 13.52 µM on Hela and 11.63 µM on MCF-7 cell lines which are comparable to the infamous anti-cancer drug, cisplatin. The cytotoxicity of this complex series increased as the ligands size extended in order of [Ru(bpy)2(L)]2+ < [Ru(phen)2(L)]2+ < [Ru(dppz)2(L)]2+.

Keywords: ruthenium, cytotoxicity, molecular light-switch, anticancer

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Authors: Aruma Baduge Kithma De Silva

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Haskap (Lonicera caerulea L.), also known as blue honeysuckle, is a newly commercialized berry crop in Canada. Haskap berries are rich in polyphenols, including, anthocyanins, which are known for potential health-promoting properties. Cyanidin-3-O-glucoside (C3G) is the most abundant anthocyanin of haskap berries. The compound C3G has the ability to reduce the risk of type 2 diabetes (T2D), which has become an increasingly common health issue around the world. The T2D is characterized as a metabolic disorder of hyperglycemia and insulin resistance. It has been demonstrated that C3G has anti-diabetic effects through several ways, including inhibition of dipeptidyl peptidase-4 (DPP-4), reduction of gluconeogenesis, improvement in insulin sensitivity, and inhibition of activities of carbohydrate hydrolyzing enzymes, including α-amylase and α-glucosidase. The goal of this study was to investigate the influence of variety and harvests maturity of haskap on C3G, other fruit quality characteristics and anti-diabetic activities of haskap berries using in vitro studies. The polyphenols present in four commercially grown haskap cultivars, Aurora, Rebecca, Larissa, and Evie harvested at five harvesting dates (H1-H5) apart from 2-3 days, were extracted separately. High-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS) analyzes of polyphenols revealed that haskap berries contain predominantly anthocyanins, flavonols, flavan-3-ols, and phenolic acids. The compound C3G was the most prominent anthocyanin, which is available in approximately 79% of total anthocyanin in four cultivars. The Larissa at H5 contained the highest C3G content. The antioxidant capacity of Evie at H5 was greater than other cultivars. Furthermore, Larissa H5 showed the greatest inhibition of carbohydrate hydrolyzing enzymes including alpha-glucosidase and alpha-amylase. In conclusion, the haskap variety and harvesting date influenced the polyphenol composition and biological properties. The variety Larissa, at H5 harvesting date, contained the highest polyphenol content and the ability of inhibition of the carbohydrate hydrolyzing enzyme as well as DPP4 enzyme in order to reduce type 2 diabetes.

Keywords: anthocyanin, Haskap, type 2 diabetes, polyphenol

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Authors: Shameel Pervez, Saad Aziz Durrani, Ibatsam Khokhar

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Pectinase is an enzyme that breaks down pectin, a compound responsible for structural integrity of the plant. Pectin is difficult to break down mechanically and the cost is very high, that is why many industries including food industries use pectinase enzyme produced by microbes for pectin breakdown. Apple (Malus domestica) is an important fruit in terms of market value. Every year, millions of apples are wasted due to post-harvest rot caused by fungi. Fungi are natural decomposers of our ecosystem and are infamous for post-harvest rot of apple fruit but at the same time they are prized for their high production of valuable extracellular enzymes such as pectinase. In this study, fungi belonging to different genus were isolated from rotten apples. Rotten samples of apple were picked from different markets of Lahore. After surface sterilization, the rotten parts were cut into small pieces and placed onto MEA media plates for three days. Afterwards, distinct colonies were picked and purified by sub-culturing. The isolates were identified to genus level through the study of basic colony morphology and microscopic features. The isolates were then subjected to screening for pectinase activity on MS media to compare pectinase production and were then subsequently tested for pathogenic activity through wound suspension method to evaluate the pathogenic activity of isolates in comparison with their pectinolytic activity. A total of twelve fungal strains were isolates from rotten apples. They were belonging to genus Penicillium, Alternaria, Paecilomyces and Rhizopus. Upon screening for pectinolytic activity, isolates Pen 1, Pen 4, and Rz showed high pectinolytic activity and were further subjected to DNA isolation and partial sequencing for species identification. The results of partial sequencing were combined with in-depth study of morphological features revealing Pen 1 as Penicillium janthinellum, Pen 4 as Penicillium griseofulvum, and Rz as Rhizopus microsporus. Pathogenic activity of all twelve isolates was evaluated. Penicillium spp. were highly pathogenic and destructive and same was the case with Paecilomyces sp. and Rhizopus sp. However, Alternaria spp. were found to be more consistent in their pathogenic activity, on all types of apples.

Keywords: apple, pectinase, fungal pathogens, penicillium, rhizopus

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