Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5194

Search results for: antiproliferative activity

5194 γ-Irradiation of Oat β- Glucan: Effect on Antioxidant and Antiproliferative Properties

Authors: Asima Shah, F. A. Masoodi, Adil Gani, Bilal Ahmad Ashwar

Abstract:

The present study was designed to evaluate the effect of γ-rays on the antioxidant and antiproliferative potential of β-glucan isolated from oats. The β-glucan was irradiated with 0, 2, 6, and 10 kGy by gamma ray. The samples were characterized by FT-IR, GPC, and quantitative estimation by Megazyme β-glucan assay kit. The average molecular weight of non-irradiated β-glucan was 199 kDa that decreased to 70 kDa at 10 kGy. Both FT-IR spectrum and chemical analysis revealed that the extracted β-glucan was pure having minor impurities. Antioxidant activity was evaluated by DPPH, lipid peroxidation, reducing power, metal chelating ability and oxidative DNA damage assays. Results revealed that the antioxidant activity of β-glucan increased with the increase in irradiation dose. Irradiated β-glucan also exhibited dose dependent cancer cell growth inhibition with irradiation doses. The study revealed that low molecular weight β-glucan with enhanced antioxidant and antiproliferative activities can be produced by a simple irradiation method.

Keywords: γ-irradiation, antioxidant activity, antiproliferative activity, β-glucan, oats

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5193 Synthesis and Antiproliferative Activity of 5-Phenyl-N3-(4-fluorophenyl)-4H-1,2,4-triazole-3,4-diamine Derivatives

Authors: L. Mallesha, P. Mallu, B. Veeresh

Abstract:

In the present study, 2, 6-diflurobenzohydrazide and 4-fluorophenylisothiocyanate were used as the starting materials to synthesize 5-phenyl-N3-(4-fluorophenyl)-4H-1, 2, 4-triazole-3, 4-diamine. Further, compound 5-phenyl-N3-(4-fluorophenyl)-4H-1, 2, 4-triazole-3,4-diamine reacted with fluoro substituted benzaldehydes to yield a series of Schiff bases. All the final compounds were characterized using IR, 1H NMR, 13C NMR, MS and elemental analyses. New compounds were evaluated for their antiproliferative effect using the MTT assay method against four human cancer cell lines (K562, COLO-205, MDA-MB231, and IMR-32) for the time period of 24 h. Among the series, few compounds showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.

Keywords: Schiff bases, MTT assay, antiproliferative activity, human cancer cell lines, 1, 2, 4-triazoles

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5192 Synthesis of [1-(Substituted-Sulfonyl)-Piperidin-4-yl]-(2,4-Difluoro-Phenyl)-Methanone Oximes and Their Biological Activity

Authors: L. Mallesha, C. S. Karthik, P. Mallu

Abstract:

A series of new [1-(substituted-benzoyl)-piperidin-4-yl]-(2,4-difluoro-phenyl)-methanone oxime derivatives, 3(a-f) were synthesized and characterized by different spectral studies. All compounds were evaluated for their in vitro antibacterial activity against bacterial strains. These compounds were screened for their antioxidant activity by DPPH• and Fe2+ chelating assay. Antiproliferative effects were evaluated using the MTT assay method against two human cancer cell lines and one astrocytoma brain tumor cell line. Compound 3b exhibited moderate antibacterial activity when compared with other compounds. All the compounds showed antioxidant activity, where compound 3f was the best radical scavenger and Fe2+ ion scavenger. Compounds, 3b, and 3d showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.

Keywords: Piperidine, antibacterial, antioxidant, antiproliferative

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5191 Anti-Cancerous Activity of Sargassum siliquastrum in Cervical Cancer: Choreographing the Fly's Danse Macabre

Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

Abstract:

Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation

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5190 A Prenylflavanoid, HME5 with Antiproliferative Activity in Human Ovarian Cancer Cells

Authors: Mashitoh Abd Rahman, Najihah Mohd Hashim, Faiqah Ramli, Syam Mohan, Noraziah Nordin, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Ovarian cancer is the most lethal gynecological malignancies. HME5, a prenylflavanoid has been isolated from local medicinal plant. This compound has been reported to possess a broad spectrum of biological activities including anticancer property. However, the potential of HME5 as an antiproliferative and cytotoxic agent on an ovarian cancer cells has not yet been investigated. In this present study, we examined the antiproliferative and cytotoxic effect of HME5 on Caov-3 (Human Ovarian Adenocarcinoma) cell line by using 3-[4,5-dimethylthizol-2-y]-2,5-diphenyltetrazolium bromide (MTT) assay, Acridine orange and propidium Iodide (AOPi) and cell cycle analysis study. HME5 has shown to inhibit Caov-3 in a time-dependent manner with the IC50 values of 5µg/ml, 2µg/ml and 1µg/ml after 24h, 48h and 72h treatment, respectively. Morphological study from AOPi analysis showed that HME5 induced apoptosis after 24 and 48h post-treatment. Nevertheless, HME5 exhibited cell cycle arrest at G1 phase as indicated in flow cytometry cell cycle profiling. In conclusion, HME5 inhibited proliferation of Caov-3 through induction of apoptosis and cell cycle arrest at G1 phase.

Keywords: apoptosis, prenylflavanoid, ovarian cancer, HME5

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5189 New Bioactive Compounds from Two Chrysanthemum Saharian Species (Asteraceae) Growing in Algeria

Authors: Zahia Kabouche, Ouissem Gherboudj, Naima Boutaghane, Ahmed Kabouche, Laurence Voutquenne-Nazabadioko

Abstract:

Chrysanthemum herbs (Asteraceae) are extensively used as food additives and in folk medicine. Anti-cancer, anti-human immunodeficiency virus type 1 (HIV-1), anti-inflammatory, antinociceptive and antiproliferative activities as well as antioxidant effects have been reported for Chrysanthemum species. We report the isolation and identification of flavonoids and new and known terpenoids from the endemic species, C. macrocarpum and C. deserticolum “guertoufa”, used in Algerian Sahara as tea drinks and in “couscous” and soups “Chorba”. Structures of the isolated compounds were established by 1-D and 2-D homo and hetero-nuclear NMR (1H, 13C, COSY, HSQC, HMBC, and NOESY), mass spectrometry, UV and comparison with literature data. C. deserticolum extracts were tested by four methods to identify the antioxidant activity namely, ABTS•+, DPPH• scavenging, CUPRAC and ferrous-ions chelating activity methods. Anti-inflammatory, antinociceptive, antiproliferative and antioxidant activities of C. macrocarpum extracts and isolated compounds are also reported here.

Keywords: Chrysanthemum macrocarpum, C. deserticolum, flavonoids, terpenoids, antioxidant, anti-inflammatory, anti-proliferative

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5188 Chromatographic Lipophilicity Determination of Newly Synthesized Steroid Derivatives for Further Biological Analysis

Authors: Milica Z. Karadzic, Lidija R. Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Z. Kovacevic, Anamarija I. Mandic, Katarina Penov-Gasi, Andrea R. Nikolic, Aleksandar M. Okljesa

Abstract:

In this study, a set of 29 newly synthesized steroid derivatives were investigated using reversed-phase high-performance liquid chromatography (RP-HPLC) as a first step in preselection of drug candidates. This analysis presents an experimental determination of chromatographic lipophilicity, and it was conducted to obtain physicochemical characterization of these molecules. As the most widely used bonded phases in RP-HPLC, octadecyl (C18) and octyl (C8) were used. Binary mixtures of water and acetonitrile or methanol were used as mobile phases. Obtained results were expressed as retention factor values logk and they were correlated with logP values. The results showed that both columns provide good estimations of the chromatographic lipophilicity of the molecules included in this study. This analysis was conducted in order to characterize newly synthesized steroid derivatives for further investigation regarding their antiproliferative and antimicrobial activity. This article is based upon work from COST Action (CM1306), supported by COST (European Cooperation in Science and Technology).

Keywords: antiproliferative activity, chromatographic lipophilicity, liquid chromatography, steroids

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5187 Metabolites of Polygonum L. Plants Having Antitumor Properties

Authors: Dmitriy Yu. Korulkin, Raissa A. Muzychkina

Abstract:

The article represents the results of research of antitumor activity of different structural types of plant flavonoids extracted by authors from Polygonum L. plants in commercial reserves at the territory of the Republic of Kazakhstan. For the first time ever the results comparative research of antitumor activity of plant flavonoids of different structural groups and their synthetic derivatives have been represented. The results of determination of toxicity of flavonoids in single parenteral infusion conditions have been represented. Experimental substantiation of possible mechanisms of antiproliferative and cytotoxic action of flavonoids has been suggested. The perspectives of usage of plant flavonoids as medications and creation of effective dosage forms of antitumor medicines on their basis have been substantiated.

Keywords: antitumor activity, cytotoxicity, flavonoids, Polygonum L., secondary metabolites

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5186 New Quinazoline Derivative Induce Cytotoxic Effect against Mcf-7 Human Breast Cancer Cell

Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

Abstract:

New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

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5185 Discovery, Design and Synthesis of Some Novel Antitumor 1,2,4-Triazine Derivatives as C-Met Kinase Inhibitors

Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

Abstract:

The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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5184 Assessment of Isatin as Surface Recognition Group: Design, Synthesis and Anticancer Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors

Authors: Harish Rajak, Kamlesh Raghuwanshi

Abstract:

Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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5183 Apoptosis Activity of Persea declinata (Bl.) Kosterm Bark Methanolic Crude Extract

Authors: P. Narrima, C. Y. Looi, M. A. Mohd, H. M. Ali

Abstract:

Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Keywords: antiproliferative, apoptosis, MCF-7 human breast cancer, Persea declinata

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5182 Effects of Fatty Acid Salts and Spices on Dermatophagoides farinae

Authors: Yumeho Obata, Mariko Era, Takayoshi Kawahara, Takahide Kanyama, Hiroshi Morita

Abstract:

Dermatophagoides farinae is major mite allergens in indoors. D. farinae is often swarm over powder products (e.g. wheat flour), because it feeds on starch or protein that are included in them. Eating powder products which are mixed D.farinae causes various allergic symptoms. Therefore, the creation of food additive agents with high safety and control of mite effect is required. Fatty acid salts and spices are known that have pesticidal activities. This study describes the effects of fatty acid salts and spices against Dermatophagoides farinae. Materials and Methods: Potassium salts of 9 fatty acids (C4:0, C6:0, C8:0, C10:0, C12:0, C14:0, C18:1, C18:2, C18:3) were prepared by mixing the fatty acid with the appropriate amount of KOH solution to a concentration of 175 mM and pH 10.5. C12Cu and C12Zn were selected as other fatty acid salts. Cayenne pepper, habanero, Japanese pepper, mustard, jalapeno pepper, curry aroma and cinnamon were selected as spices. D. farina, have been cultured in laboratory. To rear the mites, double-soled dishes containing of sterilized food were put on the big plastic container (30.0 × 20.0 × 20.0cm) which had 100% ammonium nitrate solution in the bottom. Plastic container was placed on incubator at 25 °C and 64 % relative humidity (RH) under dark condition. Sterilized food composed of dried bonito flakes and dried yeast (Ebios), 1:1 by weight. The antiproliferative method, sample and medium culture were mixed in double-soled dish and kept at 25 °C and 64 % RH. Decrease rates were determined 1 week and 4 week after treatment under microscope. D. farina was considered to be dead if appendages did not move when prodded with a pin. Results and Conclusions: The results show that the fatty acids potassium showed no antiproliferative effects against D. farinae. On the other hand, Japanese pepper, mustard, curry aroma and cinnamon were effective to decrease propagative rate (over 80 %) after treatment for 1 week against D. farina. Japanese pepper, curry aroma and cinnamon were effective to decrease propagative rate (approximately 100 %) after treatment for 4 weeks against D. farina. Especially, Japanese pepper and cinnamon showed the fasted and the most consecutive antiproliferative effects. These results indicate that Japanese pepper and cinnamon have high antiproliferative effects against D. farina and suggest spices will be used as a food additive agent.

Keywords: fatty acid salts, spices, antiproliferative effects, dermatophagoides farinae

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5181 Antioxidant Activity of the Algerian Traditional Kefir Supernatant

Authors: H. Amellal-Chibane, N. Dehdouh, S. Ait-Kaki, F. Halladj

Abstract:

Kefir is fermented milk that is produced by adding Kefir grains, consisting of bacteria and yeasts, to milk. The aim of this study was to investigate the antioxidant activity of the kefir supernatant and the raw milk. The Antioxidant activity assays of kefir supernatant and raw milk were evaluated by assessing the DPPH radical-scavenging activity. Kefir supernatant demonstrated high antioxidant activity (87.75%) compared to the raw milk (70.59 %). These results suggest that the Algerian kefir has interesting antioxidant activity.

Keywords: antioxidant activity, kefir, kefir supernatant, raw milk

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5180 Effect of Copper Complexes on Human Colon Carcinoma Cell Line and Human Breast Carcinoma Cell Line

Authors: Katarína Koňariková, Georgios A. Perdikaris, Lucia Andrezálová, Zdeňka Ďuračková, Lucia Laubertová, Helena Gbelcová, Ingrid Žitňanová

Abstract:

Introduction: The continuous demand for new anti-cancer drugs has stimulated chemotherapeutic research based on the use of essential metalloelements with the aim to develop potential drugs with lower toxicity and higher antiproliferative activity against tumors. Copper(II) and its complexes play an important role as suitable species for antiproliferative tests. Objectives: The central objective of the current study was to investigate the potential in vitro anti-proliferative effects of N-salicylidene-L-glutamato copper (II) complexes and molecular mechanism of apoptosis induced by tested complexes. In our project we tested N-salicylidene-L-glutamato copper (II) complexes ZK1 - [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK0 - ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O); MK1 - [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol); MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] at concentration range 0.001-100 µmol/L against human colon carcinoma cell line HT-29 and human breast carcinoma cell line MCF-7. Methods: Viability was assessed by direct counting of 0.4% trypan blue dye-excluding cells after 24, 48 and 72 hour cultivations with or without copper complex and by MTT assay. To analyze the type of cell death and its mechanism induced by our copper complex we used different methods. To distinguish apoptosis from necrosis we used electrophoretic analysis, to study the activity of caspases 8 and 9 – luminometric analysis and caspase activity 3 colorimetric assay. Results: The observed anti-proliferative effect of the copper complexes appeared to be dose-, time- and cell line- dependent. Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) than to ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)). Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex than human breast carcinoma cells MCF-7. IC50 decreased with time of incubation (24, 48 and 72h) for HT-29, but increased for MCF-7. By electrophoresis we found apoptotic cell death induced by our copper complexes in HT-29 at concentrations 1, 10, 50 and 100 µmol/L after 48h (ZK1) and 72h (MK0, MK1) and in MCF-7 we did not find apoptosis. We also studied molecular mechanism of apoptosis in HT-29 induced by copper complexes. We found active caspase 9 in HT-29 after ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)) influence and active caspase 8 after MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) influence. Conclusion: Our copper complexes showed cytotoxic activities against human colon carcinoma cells HT-29 and breast cancer cell line MCF-7 in vitro. Apoptosis was activated by mitochondrial pathway (intrinsic pathway) in case of ZK1 [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK1 [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol) and MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] copper complexes and by death receptors (extrinsic pathway) in case of MK0 [Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O copper complex in HT-29.

Keywords: apoptosis, copper complex, cancer, carcinoma cell line

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5179 Design and Synthesis of Some Pyrimidine Derivatives as Bruton’s Tyrosine Kinase Inhibitors for Hematologic Malignancies

Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

Abstract:

Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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5178 Biological Activity of Essential Oils from Salvia nemorosa L.

Authors: Abdol-Hassan Doulah

Abstract:

In this study, antimicrobial activity of essential oil and ethyl acetate and ether extracts of S. nemorosa were examined against some species of bacteria and fungi. The essential oil of the aerial part of S. nemorosa was examined by GC and GC-MS. In the essential oil of S. nemorosa 26 Compounds have been identified. 2-Nonanone (44.09 %), 2-Undecanone (33.79 %), E-Caryophyllene (3.74 %) and 2-Decanone (2.89 %) were the main components of the essential oil. The essential oil analysis showed greatest antimicrobial activity against Staphylococcus epidermidis (5.3 μg/ml) and S. cerevisiae (9.3 μg/ml). The ethyl acetate showed greatest antimicrobial activity against Bacillus subtilis (106.7 μg/ml), Candida albicans (5.3 μg/ml) and ether extract showed greatest antimicrobial activity against Klebseilla pneumoniae (10.7 μg/ml) and Saccharomyces cerevisiae (10.7 μg/ml). In conclusion, we suggest that the antimicrobial activity of S. nemorosa may be due to its content of germacrene and linalool.

Keywords: antibacterial activity, antifungal activity, Salvia nemorosa L., essential oils, biological activity

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5177 Application of Computational Chemistry for Searching Anticancer Derivatives of 2-Phenazinamines as Bcr-Abl Tyrosine Kinase Inhibitors

Authors: Gajanan M. Sonwane

Abstract:

The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet-lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet-lab experiments for synthesizing 2-phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using a semi-empirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as a PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. The parent compound 2-phenazinamine was synthesized by reduction of 2, 4-dinitro-N-phenyl-benzenamine in the presence of tin chloride followed by cyclization in the presence of nitrobenzene and magnesium sulfate. The derivatization at the amino function of 2-phenazinamine was performed by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazine-2-yl) thiazolidine-4-one. Synthesized 39 novel derivatives of 2-phenazinamine and performed antioxidant activity, anti antiproliferative on the bulb of onion and anticancer activity on cell line showing significant competition with marked blockbuster drug imatinib.

Keywords: computer-aided drug design, tyrosin kinases, anticancer, docking

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5176 Synthesis and in-vitro Evaluation of Quinozolines as Potent EGFR Inhibitor

Authors: Vinaya Kambappa, Chinnadurai Mani, Komaraiah Palle

Abstract:

Non-small cell-lung cancer (NSCLC) cells have increased expression of EGFR, which makes them a potential target for cancer therapy. Based on molecular docking and previous reports, we designed and synthesized quinazoline derivatives as potent EGFR inhibitors. Among the derivatives, three compounds showed good antiproliferative activity against A-549 and H-1299 cells. Furthermore, these compounds inhibited EGFR signaling exhibiting diminishing p-EGFR and its downstream proteins like p-Akt, p-Erk1/2, and p-mTOR; however, it did not alter the levels of EGFR, Akt, Erk1/2 and mTOR proteins. Flow cytometric analysis indicated the accumulation of cells at G1 phase suggesting induction of apoptosis, which was further confirmed by annexin V/propidium iodide staining. Our study suggested that quinazoline scaffold can be developed as novel EGFR kinase inhibitors for cancer therapy.

Keywords: apoptosis, non-small cell-lung cancer cells, EGFR, quinazoline

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5175 Cloning, Expression and N-Terminal Pegylation of Human Interferon Alpha-2b Analogs and Their Cytotoxic Evaluation against Cancer Cell Lines

Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

Abstract:

In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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5174 The Investigation of Correlation between Body Composition and Physical Activity in University Students

Authors: Ferruh Taspinar, Gulce K. Seyyar, Gamze Kurt, Eda O. Okur, Emrah Afsar, Ismail Saracoglu, Betul Taspinar

Abstract:

Alterations of physical activity can effect body composition (especially body fat ratio); however body mass index may not sufficient to indicate these minimal differences. The aim of this study was to evaluate the relationship between body composition and physical activity in university students. In this study, 132 university students (mean age; 21.21±1.51) were included. Tanita BC-418 and International Physical Activity Questionnaire (IPAQ) were used to evaluate participants. The correlation between the parameters was analysed via Spearman correlation analysis. Significance level in statistical analyses was accepted is 0.05. The results showed that there was no correlation between body mass index and physical activity (p>0.05). There was a positive correlation between body muscle ratio and physical activity, whereas a negative correlation between body fat ratio and physical activity (p<0.05). This study showed that body fat and muscle ratio affects the level of physical activity in healthy university students. Therefore, we thought that physical activity might reduce effects of the diseases caused by disturbed body composition. Further studies are required to support this idea.

Keywords: body composition, body mass index, physical activity, university student

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5173 Chemical Composition and Antioxidant Activity of Methanolic Extract of Spilanthes acmella Murr.

Authors: Wanthani Paengsri, Thanyarat Chuesaard, Napapha Promsawan

Abstract:

Spilanthes acmella Murr. was extracted with methanol, yielding methanol crude extract 5.86 %w/w. This study aimed to examine the chemical composition and antioxidant activity of methanolic crude extract. The chemical composition of methanolic crude extract was analyzed by gas chromatography-mass spectrometry (GC-MS). The predominant components were found to be palmitic acid (40.08%), 2-hexadecanoyl glycerol (6.96%) and octadecanoic acid (4.06%). Antioxidant activity was determined using 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radical, for evaluating free radicle scavenging activity. The methanolic extract at 150 µg/mL showed an antioxidant activity with high of radical scavenging activity (75.23%).

Keywords: antioxidant activity, GC-MS analysis, Spilanthes, Phak-Kratt Hauwaen

Procedia PDF Downloads 154
5172 Polyphenols Content and Antioxidant Activity of Extracts from Peganum harmala Seeds

Authors: Rachid Kacem, Sara Talbi, Yasmina Hemissi, Sofia Bouguattoucha

Abstract:

The aim of the present work is the evaluation of the antioxidant activity of the Peganum harmala (P. harmala) seeds extracts. The antioxidant activity was evaluated by applying two methods, the method of ß-carotene bleaching and DPPH (2, 2-Diphenyl-1-Picryl-Hydrazyl). Using Folin-Ciocalteu assay, these results revealed that the concentration of polyphenols in EthOH E. (122.28 ± 2.24 µg GAE/mg extract) is the highest. The antiradical activity of the P. harmala seeds extracts on DPPH was found to be dose dependent with polyphenols concentration. The E. EthOH extract showed the highest antioxidant activity (IC = 252.10 ± 11.18 μg /ml). The test of β-carotene bleaching indicates that the E. EthOH of P. harmala showed the highest percentage of the antioxidant activity (49.88 %).

Keywords: antioxidant activity, Peganum harmala, polyphenols, flavonoids

Procedia PDF Downloads 363
5171 The Effect of Solution pH of Chitosan on Antimicrobial Properties of Nylon 6,6 Fabrics

Authors: Nilüfer Yıldız Varan

Abstract:

The antimicrobial activities of chitosan against various bacteria and fungi are well known, and the antimicrobial activity of chitosan depends on pH. This study investigates the antimicrobial activity at different pH levels. Nylon 6,6 fabrics were treated with different chitosan solutions. Additionally, samples were treated also in basic conditions to see the antimicrobial activities. AATCC Test Method 100 was followed to evaluate the antimicrobial activity using Staphylococcus aureus ATCC 6538 test inoculum. The pH of the chitosan solutions was controlled below 6.5 since chitosan shows its antimicrobial activity only in acidic conditions because of its poor solubility above 6.5. In basic conditions, the samples did not show any antimicrobial activity. It appears from SEM images that the bonded chitosan in the structures exists. In acidic media (ph < 6.5), all samples showed antimicrobial activity. No correlation was found between pH levels and antimicrobial activity in acidic media.

Keywords: chitosan, nylon 6, 6, crosslinking, pH stability, antimicrobial

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5170 Immune Activity of Roman Hens as Influenced by the Feed Formulated with Germinated Paddy Rice

Authors: Wirot Likittrakulwong, Pisit Poolprasert, Tossaporn Incharoen

Abstract:

Germinated paddy rice (GPR) has the potential to be used as a feed ingredient. However, their properties have not been fully investigated. This paper examined the nutrient digestibility and the relationship to immune activity in Roman hens fed with GPR. It was found that true and apparent metabolizable energy (ME) values of GPR were 3.20 and 3.28 kcal/g air dry, respectively. GPR exhibited high content of phytonutrients, especially GABA. GPR showed similar protein profiles in comparison to non-germinated paddy rice. For immune activity, the feed with GPR enhanced the immune activity of Roman hens under high stocking density stress as evidenced by the activity of superoxide dismutase (SOD) and lysozyme activity. In this study, GPR is proved to be a good source of functional ingredient for chicken feed.

Keywords: germinated paddy rice, nutrient digestibility, immune activity, functional property

Procedia PDF Downloads 78
5169 Activity Data Analysis for Status Classification Using Fitness Trackers

Authors: Rock-Hyun Choi, Won-Seok Kang, Chang-Sik Son

Abstract:

Physical activity is important for healthy living. Recently wearable devices which motivate physical activity are quickly developing, and become cheaper and more comfortable. In particular, fitness trackers provide a variety of information and need to provide well-analyzed, and user-friendly results. In this study, frequency analysis was performed to classify various data sets of Fitbit into simple activity status. The data from Fitbit cloud server consists of 263 subjects who were healthy factory and office workers in Korea from March 7th to April 30th, 2016. In the results, we found assumptions of activity state classification seem to be sufficient and reasonable.

Keywords: activity status, fitness tracker, heart rate, steps

Procedia PDF Downloads 294
5168 A New Phenolic Compound Isolated from Laurus nobilis from Lebanon and Comparison of Antioxidant Activity of Different Parts

Authors: Turk Ayman, Ahn Jong Hoon, Khalife K. Hala, Gali-Muhtasib Hala, Lee Mi Kyeong

Abstract:

Laurus nobilis is an aromatic plant widely distributed in the Mediterranean region. The leaves of this plant are frequently used as a spice and as a traditional medicine for several diseases. In our present study, the methanolic extract of L. nobilis leaves showed antioxidant activity. Chromatographic separations of the EtOAc fraction which had the highest antioxidant activity led to the isolation of 12 compounds. Among them, there was a new phenylpropanoid derivative, which was identified by 1D and 2D NMR experiments, as well as high resolution mass spectrometry. In addition, two major compounds, catechin and epicatechin, which showed strong antioxidant activity may be responsible for the antioxidant activity of L. nobilis leaves. Since different plant parts may contain different types of constituents which contribute to the biological activities, we investigated the antioxidant activity of different parts of L. nobilis such as leaves, stems and fruits. Stems of L. nobilis showed the most potent antioxidant activity, followed by leaves. Further quantitation of total phenol and flavonoids contents revealed a positive correlation between the content of these compounds and antioxidant activity. Taken together, phenolic compounds including flavonoids are responsible for antioxidant activity of L. nobilis. In addition, stem parts of L. nobilis are suggested as good sources for antioxidant activity. Conclusively, L. nobilis might be effective in several free radical mediated diseases.

Keywords: antioxidant activity, different parts, Laurus nobilis, phenolic compound

Procedia PDF Downloads 178
5167 Level of Physical Activity and Physical Fitness, and Attitudes towards Physical Activity among Senior Medical Students of Sultan Qaboos University, Sultanate of Oman

Authors: Hajar Al Rajaibi, Kawla Al Toubi, Saeed Al Jaadi, Deepali Jaju, Sanjay Jaju

Abstract:

Background: The available evidence in Oman on lack of physical activity call for immediate intervention. Physical activity counseling by doctors to their patients is influenced by their attitudes and personal physical fitness. To our best knowledge, the physical activity status of Omani medical students has not been addressed before. These future doctors will have a critical role in improving physical activity in patients and thus their overall health. Objective: The aim of the study is to assess the physical activity level, physical fitness level, and attitudes towards physical activity among Sultan Qaboos University senior medical students. Methods: In this cross-sectional study (N=110; males 55), physical activity level was assessed using International Physical Activity Questionnaire (IPAQ ) short form and attitudes towards physical activity using a fifty-four-items Kenyon questionnaire. The physical fitness level was assessed by estimating maximal oxygen uptake (VO₂max) using Chester step test. Results: Female students reported more sitting time more than 7hr/day (85.5%) compared to male students (40%; p < 0.05). The IPAQ revealed moderate level of physical activity in 58% of students. Students showed a high positive attitude towards physical activity for health and fitness and low attitude for physical activity as tension and risk. Both female and male students had a similar level and attitude towards physical activity. Physical fitness level was excellent (VO₂max > 55ml O₂/kg/min) in 11% of students, good (VO₂max>44-54ml O₂/kg/min) in 49% and average to below-average in 40%. Objectively measured physical fitness level, subjectively reported physical activity level or attitudes towards physical activity were not correlated. Conclusion: Omani medical students have a positive attitude towards physical activity but moderate physical activity level. Longer sitting time in females need further evaluation. Efforts are required to understand reasons for present physical activity level and to promote good physical activity among medical students by creating more awareness and facilities.

Keywords: Chester step test, Kenyon scale, medical students, physical activity, physical fitness

Procedia PDF Downloads 76
5166 Performance of Bimetallic Catalyst in the Oxidation of Volatile Organic Compounds

Authors: Faezeh Aghazadeh

Abstract:

The catalytic activity of Pt/γ-Al₂O₃ and Pt-Fe/γ-Al₂O₃ catalysts was investigated to bring about the complete oxidation of 2-Propanol. Among them, Pt-Fe/γ-Al₂O₃ was found to be the most promising catalyst based on activity. The catalysts were characterized by (XRD), (SEM), (TEM) and ICP-AES techniques. Iron loadings on Pt/γ-Al₂O₃ had a great effect on catalytic activity, and Pt-Fe/γ-Al₂O₃ (1.75 wt% Fe) catalyst at calcination temperature 300°C was observed to be the most active, which might be contributed to the favorable synergetic effects between Pt and Fe, high activity and the well-dispersed bimetallic phase. The combustion of 2-Propanol in the vapor phase was carried out in a conventional flow U-shape glass reactor used in the differential mode at atmospheric pressure. 2-Propanol was analyzed by a gas chromatograph VARIAN 3800 CX equipped with an FID. As observed, better performance and activity were observed for Pt-Fe/Al₂O₃ bimetallic catalyst. These results indicate that the high dispersion on support gives a positive effect on catalytic activity.

Keywords: volatile organic compounds, bimetallic catalyst, catalytic activity, low temperature

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5165 In Vitro Antifungal Activity of Essential Oil Artemisia Absinthium

Authors: Bouchenak Fatima, Lmegharbi Abdelbaki, Houssem Degaichia, Benrebiha Fatima

Abstract:

The essential oil composition of the leaf of Artemisia absinthium from region of Cherchell (The south of Algeria) was investigated by GC, GC-MS. 27 constituents were identified correspond to 84, 63% of the total oil. The major components are Thujone (60, 82%), Chamazulènel (16, 62%), ρ-cymène (4, 29%) and 2-carène (4.25%). The antimicrobial activity of oil was tested in vitro by two methods (agar diffusion and microdilution) on three plant pathogenic fungi. This oil has been tested for antimicrobial activity against three pathogenic fungi (Botrytis cinerea, Fusarium culmorum and Helminthosporium Sp.).The study of activity was evaluated by two methods: Method of diffusion in gelose and the minimum inhibitory concentration MIC. This oil exhibited an interesting antimicrobial activity. A preliminary study showed that this oil presented high toxicity against this fungus. These results, although preliminary show a good antifungal activity, to limit and inhibit stop the development of those pathogen agent.

Keywords: artemisia absinthian, extraction process, chemical study, antifungal activity

Procedia PDF Downloads 391