Search results for: binding kinetics

Authors: Chedly Tizaoui, Hussain Mohammed, Lobna Mansouri, Nidal Hilal, Latifa Bousselmi

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The degradation of diethyl phthalate (DEP) was studied using heterogeneous catalytic ozonation. Activated carbon was used as a catalyst. The degradation of DEP with ozone alone was slow while catalytic ozonation increased degradation rates. Second-order reaction kinetics was used to describe the experimental data, and the corresponding rate constant values were 1.19 and 3.94 M-1.s-1 for ozone and ozone/activated carbon respectively.

Keywords: ozone, heterogeneous catalytic ozonation, diethyl phthalate, endocrine disrupting chemicals

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Authors: A. S. Lunev, A. A. Larenkov, O. E. Klementyeva, G. E. Kodina

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Background and aims: 68Ga-citrate is one of prospective radiopharmaceutical for PET-imaging of inflammation and infection. 68Ga-citrate is 67Ga-citrate analogue using since 1970s for SPECT-imaging. There's known rebinding reaction occurs past Ga-citrate injection and gallium (similar iron Fe3+) binds with blood transferrin. Then radiolabeled protein complex is delivered to pathological foci (inflammation/infection sites). But excessive gallium bindings with transferrin are cause of slow blood clearance, long accumulation time in foci (24-72 h) and exception of application possibility of the short-lived gallium-68 (T½ = 68 min). Injection of additional chemical agents (e.g. Fe3+ compounds) competing with radioactive gallium to the blood transferrin joining (blocking of its metal binding capacity) is one of the ways to solve formulated problem. This phenomenon can be used for correction of 68Ga-citrate pharmacokinetics for increasing of the blood clearance and accumulation in foci. The aim of real studying is research of effect of stable Fe-citrate on 68Ga-citrate tissue distribution. Materials and methods: 68Ga-citrate without/with extra injection of stable Fe-citrate (III) was injected nonlinear mice with inflammation models (aseptic soft tissue inflammation, lung infection, osteomyelitis). PET/X-RAY Genisys4 (Sofie Bioscience, USA) was used for non-invasive PET imaging (for 30, 60, 120 min past injection 68Ga-citrate) with subsequent reconstruction of imaging and their analysis (value of clearance, distribution volume). Scanning time is 10 min. Results and conclusions: I. v. injection of stable Fe-citrate blocks the metal-binding capability of transferrin serum and allows decreasing gallium-68 radioactivity in blood significantly and increasing accumulation in inflammation (3-5 time). It allows receiving more informative PET-images of inflammation early (for 30-60 min after injection). Pharmacokinetic parameters prove it. Noted there is no statistically significant difference between 68Ga-citrate accumulation for different inflammation model because PET imaging is indication of pathological processes and is not their identification.

Keywords: 68Ga-citrate, Fe-citrate, PET imaging, mice, inflammation, infection

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Authors: Diwan Singh

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The ability of non-living Spirogyra sp. biomass for biosorption of copper(II) ions from aqueous solutions was explored. The effect of contact time, pH, initial copper ion concentration, biosorbent dosage and temperature were investigated in batch experiments. Both the Freundlich and Langmuir Isotherms were found applicable on the experimental data (R2>0.98). Qmax obtained from the Langmuir Isotherms was found to be 28.7 mg/g of biomass. The values of Gibbs free energy (ΔGº) and enthalpy change (ΔHº) suggest that the sorption is spontaneous and endothermic at 20ºC-40ºC.

Keywords: biosorption, Spirogyra sp., contact time, pH, dose

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Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

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Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

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Authors: John Olorunfemi Abe, Olawale Muhammed Popoola, Abimbola Patricia Idowu Popoola

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Hydrogen is an appealing alternative to fossil fuels because of its abundance, low weight, high energy density, and relative lack of contaminants. However, its low density presents a number of storage challenges. Therefore, this work studies the influence of refractory nitride additives consisting of 5 wt. % each of hexagonal boron nitride (h-BN), titanium nitride (TiN), and aluminum nitride (AlN) on hydrogen storage and electrochemical characteristics of Ti6Al4V-based materials produced by spark plasma sintering. The microstructure and phase constituents of the sintered materials were characterized using scanning electron microscopy (in conjunction with energy-dispersive spectroscopy) and X-ray diffraction, respectively. Pressure-composition-temperature (PCT) measurements were used to assess the hydrogen absorption/desorption behavior, kinetics, and storage capacities of the sintered materials, respectively. The pure Ti6Al4V alloy displayed a two-phase (α+β) microstructure, while the modified composites exhibited apparent microstructural modifications with the appearance of nitride-rich secondary phases. It is found that the diffusion process controls the kinetics of the hydrogen absorption. Thus, a faster rate of hydrogen absorption at elevated temperatures ensued. The additives acted as catalysts, lowered the activation energy and accelerated the rate of hydrogen sorption in the composites relative to the monolithic alloy. Ti6Al4V-5 wt. % h-BN appears to be the most promising candidate for hydrogen storage (2.28 wt. %), followed by Ti6Al4V-5 wt. % TiN (2.09 wt. %), whereas Ti6Al4V-5 wt. % AlN shows the least hydrogen storage performance (1.35 wt. %). Accordingly, the developed hydride system (Ti6Al4V-5h-BN) may be competitive for use in applications involving short-range continuous vehicles (~50-100km) as well as stationary applications such as electrochemical devices, large-scale storage cylinders in hydrogen production locations, and hydrogen filling stations.

Keywords: hydrogen storage, Ti6Al4V hydride system, pressure-composition-temperature measurements, refractory nitride additives, spark plasma sintering, Ti6Al4V-based materials

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Authors: Manuel Jose Oyson

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The Intergovernmental Panel on Climate Change (IPCC) warned in its most recent report for the entire world “to both mitigate and adapt to climate change if it is to effectively avoid harmful climate impacts.” The IPCC observed “with high confidence” a more rapid rise in total anthropogenic greenhouse gas emissions (GHG) emissions from 2000 to 2010 than in the past three decades that “were the highest in human history”, which if left unchecked will entail a continuing process of global warming and can alter the climate system. Current efforts, however, to respond to the threat of global warming, such as the United Nations Framework Convention on Climate Change and the Kyoto Protocol, have focused on states, and fail to involve Transnational Corporations (TNCs) which are responsible for a vast amount of GHG emissions. Involving TNCs in the search for solutions to climate change is consistent with an acknowledgment by contemporary international law that there is an international role for other international persons, including TNCs, and departs from the traditional “state-centric” response to climate change. Putting the focus of GHG emissions away from states recognises that the activities of TNCs “are not bound by national borders” and that the international movement of goods meets the needs of consumers worldwide. Although there is no legally-binding instrument that covers TNC activities or legal responsibilities generally, TNCs have increasingly been made legally responsible under international law for violations of human rights, exploitation of workers and environmental damage, but not for climate change damage. Imposing on TNCs a legally-binding obligation to reduce their GHG emissions or a legal liability for climate change damage is arguably formidable and unlikely in the absence a recognisable source of obligation in international law or municipal law. Instead a recourse to “soft law” and non-legally binding instruments may be a way forward for TNCs to reduce their GHG emissions and help in addressing climate change. Positive effects have been noted by various studies to voluntary approaches. TNCs have also in recent decades voluntarily committed to “soft law” international agreements. This development reflects a growing recognition among corporations in general and TNCs in particular of their corporate social responsibility (CSR). While CSR used to be the domain of “small, offbeat companies”, it has now become part of mainstream organization. The paper argues that TNCs must voluntarily commit to reducing their GHG emissions and helping address climate change as part of their CSR. One, as a serious “global commons problem”, climate change requires international cooperation from multiple actors, including TNCs. Two, TNCs are not innocent bystanders but are responsible for a large part of GHG emissions across their vast global operations. Three, TNCs have the capability to help solve the problem of climate change. Assuming arguendo that TNCs did not strongly contribute to the problem of climate change, society would have valid expectations for them to use their capabilities, knowledge-base and advanced technologies to help address the problem. It would seem unthinkable for TNCs to do nothing while the global environment fractures.

Keywords: climate change law, corporate social responsibility, greenhouse gas emissions, transnational corporations

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Authors: H. K. Ratre, M. Roy, S. Roy, M. S. Parmar, V. Bhagat

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Mastitis is a common problem of dairy industries. Reduction in milk production and an irreparable damage to the udder associated with the disease are common causes of culling of dairy cows. Milk from infected animals is not suitable for drinking and for making different milk products. So, it has a major economic importance in dairy cattle. The aims of this study were to investigate the bacteriological panorama in milk from udder quarters with subclinical mastitis and to carried out for the molecular characterization of the major isolated organisms, from subclinical mastitis-affected cows in and around Durg and Rajnandgaon district of Chhattisgarh. Isolation and identification of bacteria from the milk samples of subclinical mastitis-affected cows were done by standard and routine culture procedures. A total of 78 isolates were obtained from cows and among the various bacteria isolated, Staphylococcus spp. occupied prime position with occurrence rate of 51.282%. However, other bacteria isolated includeStreptococcus spp. (20.512%), Micrococcus spp. (14.102%), E. coli (8.974%), Klebsiela spp. (2.564%), Salmonella spp. (1.282%) and Proteus spp. (1.282%). Staphylococcus spp. was isolated as the major causative agent of subclinical mastitis in the studied area. Molecular characterization of Staphylococus aureusisolates was done for genetic expression of the virulence genes like ‘nuc’ encoding thermonucleaseexoenzyme, coa and spa by PCR amplification of the respective genes in 25 Staphylococcus isolates. In the present study, 15 isolates (77.27%) out of 20 coagulase positive isolates were found to be genotypically positive for ‘nuc’ where as 20 isolates (52.63%) out of 38 CNS expressed the presence of the same virulence gene. In the present study, three Staphylococcus isolates were found to be genotypically positive for coa gene. The Amplification of the coa gene yielded two different products of 627, 710 bp. The amplification of the gene segment encoding the IgG binding region of protein A (spa) revealed a size of 220 and 253bp in twostaphylococcus isolates. The X-region binding of the spa gene produced an amplicon of 315 bp in one Staphylococcal isolates. Staphylococcus aureus was found to be major isolate (51.28%) responsible for causing subclinical mastitis in cows which also showed expression of virulence genesnuc, coa and spa.

Keywords: mastitis, bacteria, characterization, expression, gene

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: Heri Hermansyah, Annisa Kurnia, A. Vania Anisya, Adi Surjosatyo, Yopi Sunarya, Rita Arbianti, Tania Surya Utami

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Lipase is one of biocatalyst which is applied commercially for the process in industries, such as bioenergy, food, and pharmaceutical industry. Nowadays, biocatalysts are preferred in industries because they work in mild condition, high specificity, and reduce energy consumption (high pressure and temperature). But, the usage of lipase for industry scale is limited by economic reason due to the high price of lipase and difficulty of the separation system. Immobilization of lipase is one of the solutions to maintain the activity of lipase and reduce separation system in the process. Therefore, we conduct a study about lipase immobilization with the adsorption-cross linking method using glutaraldehyde because this method produces high enzyme loading and stability. Lipase is immobilized on different kind of resin with the various functional group. Highest enzyme loading (76.69%) was achieved by lipase immobilized on anion macroporous which have anion functional group (OH^‑). However, highest activity (24,69 U/g support) through olive oil emulsion method was achieved by lipase immobilized on anion macroporous-chitosan which have amino (NH₂) and anion (OH^-) functional group. In addition, it also success to produce biodiesel until reach yield 50,6% through interesterification reaction and after 4 cycles stable 63.9% relative with initial yield. While for Aspergillus, niger lipase immobilized on anion macroporous-kitosan have unit activity 22,84 U/g resin and yield biodiesel higher than commercial lipase (69,1%) and after 4 cycles stable reach 70.6% relative from initial yield. This shows that optimum functional group on support for immobilization with adsorption-cross linking is the support that contains amino (NH₂) and anion (OH^-) functional group because they can react with glutaraldehyde and binding with enzyme prevent desorption of lipase from support through binding lipase with a functional group on support.

Keywords: adsorption-cross linking, immobilization, lipase, resin

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Authors: Gábor Kocsmárik

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The topic of this is coercive measures against assets in which the factor of the procedure contains a foreign element. We speak of cross-border enforcement if the debtor or the property requesting enforcement or subject to enforcement is not located in the bordering country. Given that the jurisdiction of a country cannot extend beyond its borders, the cooperation of nations and the mutual recognition of their decisions are necessary to eliminate this. In addition, it is essential to create framework rules that are binding and enforceable for each country participating in the convention. During the study, some conventions between countries that are still in force will be presented, which can serve as a starting point for dealing with existing problems.

Keywords: law, execution, civil procedure law, international

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Alok Kumar Yadav, Saurabh Saraswat, Preeti Sirohi, Manjoo Rani, Sameer Srivastava, Manish Pratap Singh, Nand K. Singh

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The development of antibiotic resistance in bacteria is increasing at an alarming rate, and this is considered as one of the most serious threats in the history of medicine, and an alternative solution should be derived so as to tackle this problem. In many countries, people use the medicinal plants for the treatment of various diseases as these are cheaper, easily available and least toxic. Syzygium cumini is used for the treatment of various kinds of diseases but their mechanism of action is not reported. The antimicrobial activity of Syzygium cumini was tested by the well diffusion assay and zone of inhibition was reported to be 20.06 mm as compared to control with MIC of 0.3 mg/ml. Genomic DNA fragmentation of Bacillus subtilis revealed apoptosis and FE-SEM indicate cell wall cracking on several intervals of time. Propidium iodide staining results showed that few bacterial cells were stained in the control and population of stained cells increase after exposing them for various period of time. Flow cytometric kinetic data analysis on the membrane permeabilization in bacterial cell showed the significant contribution of antimicrobial potential of the seed extract on antimicrobial-induced permeabilization. Two components of Syzygium cumini methanolic seed extract was found to be quite active against four enzymes like PDB ID- 1W5D, 4OX3, 3MFD and 5E2F which have a very crucial role in membrane synthesis in Bacillus subtilis by in silico analysis. Through in silico analysis, lupeol showed highest binding energy for macromolecule 1W5D and 4OX3 whereas stigmasterol showed the highest binding energy for macromolecule 3MFD and 5E2F respectively. It showed that methanolic seed extract of Syzygium cumini can be used for the inhibition of foodborne infections caused by Bacillus subtilis and also as an alternative of prevalent antibiotics.

Keywords: antibiotics, Bacillus subtilis, inhibition, Syzygium cumini

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Authors: Tong Ming Liu

Abstract:

Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

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Authors: Diana Larisa Vladoiu, Vasile Ostafe, Adriana Isvoran

Abstract:

Molecular docking calculations reveal that pesticides provide favorable interactions with the bacterial chitinases. Pesticides interact with both hydrophilic and aromatic residues involved in the active site of the enzymes, their positions partially overlapping the substrate and the inhibitors locations. Molecular docking outcomes, in correlation with experimental literature data, suggest that the pesticides may be degraded or having an inhibitor effect on the activity of these enzymes, depending of the application dose and rate.

Keywords: chitinases, inhibition, molecular docking, pesticides

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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Authors: Dileep Maarisetty, Janaki Komandur, Saroj S. Baral

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In the current work, photocatalytic degradation of phenol was carried both in UV and visible light to find the slowest step that is limiting the rate of photo-degradation process. Characterization such as XRD, SEM, FT-IR, TEM, XPS, UV-DRS, PL, BET, UPS, ESR and zeta potential experiments were conducted to assess the credibility of catalysts in boosting the photocatalytic activity. To explore the synergy, TiO₂ was doped with graphene and alumina. The orbital hybridization with alumina doping (mediated by graphene) resulted in higher electron transfer from the conduction band of TiO₂ to alumina surface where oxygen reduction reactions (ORR) occur. Besides, the doping of alumina and graphene introduced defects into Ti lattice and helped in improving the adsorptive properties of modified photo-catalyst. Results showed that these defects promoted the oxygen reduction reactions (ORR) on the catalyst’s surface. ORR activity aims at producing reactive oxygen species (ROS). These ROS species oxidizes the phenol molecules which is adsorbed on the surface of photo-catalysts, thereby driving the photocatalytic reactions. Since mass transfer is considered as rate limiting step, various mathematical models were applied to the experimental data to probe the best fit. By varying the parameters, it was found that intra-particle diffusion was the slowest step in the degradation process. Lagergren model gave the best R² values indicating the nature of rate kinetics. Similarly, different adsorption isotherms were employed and realized that Langmuir isotherm suits the best with tremendous increase in uptake capacity (mg/g) of TiO₂-rGO-Al₂O₃ as compared undoped TiO₂. This further assisted in higher adsorption of phenol molecules. The results obtained from experimental, kinetic modelling and adsorption isotherms; it is concluded that apart from changes in surface, optoelectronic and morphological properties that enhanced the photocatalytic activity, the intra-particle diffusion within the catalyst’s pores serve as rate-limiting step in deciding the fate of photo-catalytic degradation of phenol.

Keywords: ORR, phenol degradation, photo-catalyst, rate kinetics

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Authors: E. S. Manuylovich, V. A. Astapenko, P. A. Golovinsky

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The dispersion relation binding the constant of propagation and frequency is calculated for silver cone. The evolution of the electric field of ultrashort pulse during its propagation in conical structure is considered. Increasing of electric field during pulse propagation to the top of the cone is observed. Reduction of the pulse duration at a certain distance is observed. The dependence of minimum pulse duration on initial chirp and cone angle is investigated.

Keywords: ultrashort pulses, surface plasmon polariton, dispersion, silver cone

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Authors: Eiman A. Al-Enezi, Gin Jose, Sikha Saha, Paul Millner

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Rare earth nanotechnology has gained a considerable amount of interest in the field of biosensing due to the unique luminescence properties of lanthanides. Chelating rare earth ions plays a significant role in biological labelling applications including medical diagnostics, due to their different excitation and emission wavelengths, variety of their spectral properties, sharp emission peaks and long fluorescence lifetimes. We aimed to develop a platform for biosensors based on Europium (Eu³⁺) chelates against biomarkers of cardiac injury (heart-type fatty acid binding protein; H-FABP3) and stroke (glial fibrillary acidic protein; GFAP). Additional novelty in this project is the use of synthetic binding proteins (Affimers), which could offer an excellent alternative targeting strategy to the existing antibodies. Anti-GFAP and anti-HFABP3 Affimer binders were modified to increase the number of carboxy functionalities. Europium nitrate then incubated with the modified Affimer. The luminescence characteristics of the Eu³⁺ complex with modified Affimers and antibodies against anti-GFAP and anti-HFABP3 were measured against different concentrations of the respective analytes on excitation wavelength of 395nm. Bovine serum albumin (BSA) was used as a control against the IgG/Affimer Eu³⁺ complexes. The emission spectrum of Eu³⁺ complex resulted in 5 emission peaks ranging between 550-750 nm with the highest intensity peaks were at 592 and 698 nm. The fluorescence intensity of Eu³⁺ chelates with the modified Affimer or antibodies increased significantly by 4-7 folder compared to the emission spectrum of Eu³⁺ complex. The fluorescence intensity of the Affimer complex was quenched proportionally with increased analyte concentration, but this did not occur with antibody complex. In contrast, the fluorescence intensity for Eu³⁺ complex increased slightly against increased concentration of BSA. These data demonstrate that modified Affimers Eu³⁺ complexes can function as nanobiosensors with potential diagnostic and analytical applications.

Keywords: lanthanides, europium, chelates, biosensors

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Authors: Deepshikha Verma, V. N. Rajasekharan Pillai

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The present study reports the synthesis of cyclic PNC-28 peptides with solid-phase peptide synthesis method. In the first step, we synthesize the linear PNC-28 Peptide and in the second step, we cyclize (N-to-C or head-to-tail cyclization) the linear PNC-28 peptide. The molecular formula of cyclic PNC-28 peptide is C64H88N12O16 and its m/z mass is ≈1233.64. Elemental analysis of cyclic PNC-28 is C, 59.99; H, 6.92; N, 13.12; O, 19.98. The characterization of LC-MS, CD, FT-IR, and 1HNMR has been done to confirm the successful synthesis and cyclization of linear PNC-28 peptides.

Keywords: CD, FTIR, 1HNMR, cyclic peptide

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Authors: Seema Kothari, Dinesh Panday

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An observed correlation of the reaction rates with the changes in the nature of substituent present on one of the reactants often reveals the nature of transition state. Selective oxidation of organic compounds under non-aqueous media is an important transformation in synthetic organic chemistry. Inorganic chromates and dichromates being drastic oxidant and are generally insoluble in most organic solvents, a number of different chromium (VI) derivatives have been synthesized. Benzimidazolium dichromate (BIDC) is one of the recently reported Cr(VI) reagents which is neither hygroscopic nor light sensitive being, therefore, much stable. Not many reports on the kinetics of the oxidations by BIDC are seemed to be available in the literature. In the present investigation, the kinetics and mechanism of benzyl alcohol (BA) and a number of para- and meta-substituted benzyl alcohols by benzimidazolium dichromate (BIDC), in dimethyl sulphoxide, is reported. The reactions were followed spectrophotometrically at 364 nm by monitoring the decrease in [BIDC] for up to 85-90% reaction, the temperature being constant. The observed oxidation product is the corresponding benzaldehyde. The reactions were of first order with respect to each the alcohol and BIDC. The reactions are catalyzed by proton, and the dependence is of the form: kobs = a + b[H+]. The reactions thus follow both, an acid-dependent and acid-independent paths. The oxidation of [1,1 2H2]benzyl alcohol exhibited the presence of a substantial kinetic isotope effect ( kH/kD = 6.20 at 298 K ). This indicated the cleavage of a α-C-H bond in the rate-determining step. An analysis of the temperature dependence of the deuterium isotope effect showed that the loss of hydrogen proceeds through a concerted cyclic process. The rate of oxidation of BA was determined in 19 organic solvents. An analysis of the solvent effect by Swain’s equation indicated that though both the anion and cation-solvating powers of the solvent contribute to the observed solvent effect, the role of cation-solvation is major. The rates of the para and meta compounds, at 298 K, failed to exhibit a significant correlation in terms of Hammett or Brown's substituent constants. The rates were then subjected to analyses in terms of dual substituent parameter (DSP) equations. The rates of oxidation of the para-substituted benzyl alcohols show an excellent correlation with Taft's σI and σRBA values. However, the rates for the meta-substituted benzyl alcohols show an excellent correlation with σI and σR0. The polar reaction constants are negative indicating an electron-deficient transition state. Hence the overall mechanism is proposed to involve the formation of a chromate ester in a fast pre-equilibrium and then a decomposition of the ester in a subsequent slow step via a cyclic concerted symmetrical transition state, involving hydride-ion transfer, leading to the product. The first order dependence on alcohol may be accounted in terms of the small value of the formation constant of the ester intermediate. An another reaction mechanism accounting the acid-catalysis involve the formation of a protonated BIDC prior to formation of an ester intermediate which subsequently decomposes in a slow step leading to the product.

Keywords: benzimidazolium dichromate, benzyl alcohols, correlation analysis, kinetics, oxidation

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Authors: Luciana P. Mazur, Tatiana A. Pozdniakova, Rui A. R. Boaventura, Vitor J. P. Vilar

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The principal mechanism of metal ions sequestration by brown algae involves the formation of complexes between the metal ion and functional groups present on the cell wall of the biological material. To understand the role of functional groups on copper(II) uptake by Ascophyllum nodosum, some functional groups were chemically modified. The esterification of carboxylic groups was carried out by suspending the biomass in a methanol/HCl solution under stirring for 48 h and the blocking of the sulfonic groups was performed by repeating the same procedure for 4 cycles of 48 h. The methylation of amines was conducted by suspending the biomass in a formaldehyde/formic acid solution under shaking for 6 h and the chemical modification of sulfhydryl groups on the biomass surface was achieved using dithiodipyridine for 1 h. Equilibrium sorption studies for Cu2+ using the raw and esterified algae were performed at pH 2.0 and 4.0. The experiments were performed using an initial copper concentration of 300 mg/L and algae dose of 1.0 g/L. After reaching the equilibrium, the metal in solution was quantified by atomic absorption spectrometry. The biological material was analyzed by Fourier Transform Infrared Spectroscopy and Potentiometric Titration techniques for functional groups identification and quantification, respectively. The results using unmodified algae showed that the maximum copper uptake capacity at pH 4.0 and 2.0 was 1.17 and 0.52 mmol/g, respectively. At acidic pH values most carboxyl groups are protonated and copper sorption suffered a significant reduction of 56%. Blocking the carboxylic, sulfonic, amines and sulfhydryl functional groups, copper uptake decreased by 24/26%, 69/81%, 1/23% and 40/27% at pH 2.0/4.0, respectively, when compared to the unmodified biomass. It was possible to conclude that the carboxylic and sulfonic groups are the main functional groups responsible for copper binding (>80%). This result is supported by the fact that the adsorption capacity is directly related to the presence of carboxylic groups of the alginate polymer, and the second most abundant acidic functional group in brown algae is the sulfonic acid of fucoidan that contributes, to a lower extent, to heavy metal binding, particularly at low pH.

Keywords: biosorption, brown marine macroalgae, copper, ion-exchange

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Authors: Umar Hayatu Sidik

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Application of liquid base petroleum fuel (petrol and diesel) for transportation fuel causes emissions of greenhouse gases (GHGs), while natural gas (NG) reduces the emissions of greenhouse gases (GHGs). At present, compression and liquefaction are the most matured technology used for transportation system. For transportation use, compression requires high pressure (200–300 bar) while liquefaction is impractical. A relatively low pressure of 30-40 bar is achievable by adsorbed natural gas (ANG) to store nearly compressed natural gas (CNG). In this study, adsorbents for high-pressure adsorption of methane (CH4) was prepared from coconut shells and polyetheretherketone (PEEK) using potassium hydroxide (KOH) and microwave-assisted activation. Design expert software version 7.1.6 was used for optimization and prediction of preparation conditions of the adsorbents for CH₄ adsorption. Effects of microwave power, activation time and quantity of PEEK on the adsorbents performance toward CH₄ adsorption was investigated. The adsorbents were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric (TG) and derivative thermogravimetric (DTG) and scanning electron microscopy (SEM). The ideal CH4 adsorption capacities of adsorbents were determined using volumetric method at pressures of 5, 17, and 35 bar at an ambient temperature and 5 oC respectively. Isotherm and kinetics models were used to validate the experimental results. The optimum preparation conditions were found to be 15 wt% amount of PEEK, 3 minutes activation time and 300 W microwave power. The highest CH4 uptake of 9.7045 mmol CH4 adsorbed/g adsorbent was recorded by M33P15 (300 W of microwave power, 3 min activation time and 15 wt% amount of PEEK) among the sorbents at an ambient temperature and 35 bar. The CH4 equilibrium data is well correlated with Sips, Toth, Freundlich and Langmuir. Isotherms revealed that the Sips isotherm has the best fit, while the kinetics studies revealed that the pseudo-second-order kinetic model best describes the adsorption process. In all scenarios studied, a decrease in temperature led to an increase in adsorption of both gases. The adsorbent (M33P15) maintained its stability even after seven adsorption/desorption cycles. The findings revealed the potential of coconut shell-PEEK as CH₄ adsorbents.

Keywords: adsorption, desorption, activated carbon, coconut shells, polyetheretherketone

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Bhargav Baruah, Ali Shemsedin Reshad, Pankaj Tiwari

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This work presents a detailed study on the thermal degradation kinetics of co-pyrolysis of oil shale of Upper Assam, India with rubber seed shell, and lab-scale pyrolysis to investigate the influence of pyrolysis parameters on product yield and composition of products. The physicochemical characteristics of oil shale and rubber seed shell were studied by proximate analysis, elemental analysis, Fourier transform infrared spectroscopy and X-ray diffraction. The physicochemical study showed the mixture to be of low moisture, high ash, siliceous, sour with the presence of aliphatic, aromatic, and phenolic compounds. The thermal decomposition of the oil shale with rubber seed shell was studied using thermogravimetric analysis at heating rates of 5, 10, 20, 30, and 50 °C/min. The kinetic study of the oil shale pyrolysis process was performed on the thermogravimetric (TGA) data using three model-free isoconversional methods viz. Friedman, Flynn Wall Ozawa (FWO), and Kissinger Akahira Sunnose (KAS). The reaction mechanisms were determined using the Criado master plot. The understanding of the composition of Indian oil shale and rubber seed shell and pyrolysis process kinetics can help to establish the experimental parameters for the extraction of valuable products from the mixture. Response surface methodology (RSM) was employed usinf central composite design (CCD) model to setup the lab-scale experiment using TGA data, and optimization of process parameters viz. heating rate, temperature, and particle size. The samples were pre-dried at 115°C for 24 hours prior to pyrolysis. The pyrolysis temperatures were set from 450 to 650 °C, at heating rates of 2 to 20°C/min. The retention time was set between 2 to 8 hours. The optimum oil yield was observed at 5°C/min and 550°C with a retention time of 5 hours. The pyrolytic oil and gas obtained at optimum conditions were subjected to characterization using Fourier transform infrared spectroscopy (FT-IR) gas chromatography and mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR).

Keywords: Indian oil shale, rubber seed shell, co-pyrolysis, isoconversional methods, gas chromatography, nuclear magnetic resonance, Fourier transform infrared spectroscopy

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Kotbia Labiod, Mohamed Mouldi Tlili

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The presence of different mineral salts in natural waters may precipitate and form hard deposits in water distribution systems. In this respect, we have developed numerous works on scaling by Algerian water with a very high hardness of 102 °F. The aim of our work is to study the influence of water dynamics and its composition on mineral salts on the precipitation of calcium carbonate (CaCO3). To achieve this objective, we have adopted two precipitation techniques based on controlled degassing of dissolved CO2. This study will identify the causes and provide answers to this complex phenomenon.

Keywords: calcium carbonate, controlled degassing, precipitation, scaling

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Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn

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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.

Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins

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Authors: P. S. D. Perera, S. U. Adikary

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The gelation behavior of Chitosan/nanohydroxyapatite sol in the presence of a crosslinking agent Na ₂CO₃ was investigated experimentally. In this case, the gelation time(tgel) was determined by the rheological measurements of the final mixture. The tgel has been determined from dynamic viscosity slope experiments. We found that chitosan/nHA sol with 1% nano-hydroxyapatite and 1.6% Na2CO3 required coagulant performance. Hence Na ₂CO₃ and nanohydroxyapatite concentrations remain constant over the experiment. The order of reaction was first order with respect to chitosan and rate constant of the gel system was 9.0 x 10-4 s-1, respectively, depending on the temperature of the system. The gelation temperature was carried out at 37 ⁰C.

Keywords: kinetics, gelation, sol-gel system, chitosan/ nHA/ Na ₂CO₃ composite

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: A. Gilewska, J. Masternak, K. Kazimierczuk, L. Turlej, J. Wietrzyk, B. Barszcz

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Platinum-based drugs are now widely used as chemotherapeutic agents. However the platinum complexes show the toxic side-effects: i) the development of platinum resistance; ii) the occurrence of severe side effects, such as nephro-, neuro- and ototoxicity; iii) the high toxicity towards human fibroblast. Therefore the development of new anticancer drugs containing different transition-metal ions, for example, ruthenium, rhodium, iridium is a valid strategy in cancer treatment. In this paper, we reported the synthesis, spectroscopic, structural and biological properties of complexes of ruthenium, rhodium, and iridium containing N,N-chelating ligand (2,2’-bisimidazole). These complexes were characterized by elemental analysis, UV-Vis and IR spectroscopy, X-ray diffraction analysis. These complexes exhibit a typical pseudotetrahedral three-legged piano-stool geometry, in which the aromatic arene ring forms the seat of the piano-stool, while the bidentate 2,2’-bisimidazole (ligand) and the one chlorido ligand form the three legs of the stool. The spectroscopy data (IR, UV-Vis) and elemental analysis correlate very well with molecular structures. Moreover, the cytotoxic activity of the complexes was carried out on human cancer cell lines: LoVo (colorectal adenoma), MV-4-11 (myelomonocytic leukaemia), MCF-7 (breast adenocarcinoma) and normal healthy mouse fibroblast BALB/3T3 cell lines. To predict a binding mode, a potential interaction of metal complexes with calf thymus DNA (CT-DNA) and protein (BSA) has been explored using UV absorption and circular dichroism (CD). It is interesting to note that the investigated complexes show no cytotoxic effect towards the normal BALB/3T3 cell line, compared to cisplatin, which IC₅₀ values was determined as 2.20 µM. Importantly, Ru(II) displayed the highest activity against HL-60 (IC₅₀ 4.35 µM). The biological studies (UV-Vis and circular dichroism) suggest that arene-complexes could interact with calf thymus DNA probably via an outside binding mode and interact with protein (BSA).

Keywords: ruthenium(II) complex, rhodium(III) complex, iridium(III) complex, biological activity

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