Amino Acid Interactions Research Articles

Piceatannol improved cerebral blood flow and attenuated JNK3 and mitochondrial apoptotic pathway in a global ischemic model to produce neuroprotection.

Cerebral ischemia is one of the leading causes of death and disability worldwide. The only FDA-approved treatment is recanalization with systemic tissue plasminogen activators like alteplase, although reperfusion caused by recanalization can result in neuroinflammation, which can cause brain cell apoptosis. Therefore, after an ischemic/reperfusion injury, interventions are needed to minimize the neuroinflammatory cascade. In the present study, piceatannol (PCT) was studied for its neuroprotective efficacy in a rat model of global ischemic injury by attenuating c-Jun N-terminal kinase 3 (JNK3) downstream signaling. PCT is a resveratrol analog and a polyphenolic stilbenoid naturally occurring in passion fruit and grapes. The neuroprotective efficacy of PCT (1, 5, 10 mg/kg) in ischemic conditions was assessed through pre- and post-treatment. Cerebral blood flow (CBF) and tests for functional recovery were assessed. Protein and gene expression were done for JNK3 and other inflammatory markers. A docking study was performed to identify the amino acid interaction. The results showed that PCT improved motor and memory function as measured by a functional recovery test believed to be due to an increase in cerebral blood flow. Also, the caspase signaling which promotes apoptosis was found to be down-regulated; however, nitric oxide synthase expression was up-regulated, which could explain the enhanced cerebral blood flow (CBF). According to our findings, PCT impeded c-Jun N-terminal kinase 3 (JNK3) signaling by suppressing phosphorylation and disrupting the mitochondrial apoptotic pathway, which resulted in the neuroprotective effect. Molecular docking analysis was performed to investigate the atomic-level interaction of JNK3 and PCT, which reveals that Met149, Leu206, and Lys93 amino acid residues are critical for the interaction of PCT and JNK3. According to our current research, JNK3 downstream signaling and the mitochondrial apoptosis pathway are both inhibited by PCT, which results in neuroprotection under conditions of global brain ischemia. Piceatannol attenuated JNK3 phosphorylation during the ischemic condition and prevented neuronal apoptosis.

To the Issue of the Complementarity of Biomolecules in the Space of the Highest Dimension

Peculiarities of the conditions of correspondence of biomolecules of higher dimension, necessary for the passage of chemical reactions between them, are considered. As specific examples, the interactions of amino acids with each other and nucleic acids with each other are considered. It is shown that in the case of chemical interaction of biomolecules of higher dimension, the conditions of correspondence (complementarity) are associated with a mirror image of the geometric elements of the corresponding polytopes of higher dimension.

Exploring Intra- and Inter-Regional Interactions in the IDP α-Synuclein Using smFRET and MD Simulations.

Theoretical concepts from polymer physics are often used to describe intrinsically disordered proteins (IDPs). However, amino acid interactions within and between regions of the protein can lead to deviations from typical polymer scaling behavior and even to short-lived secondary structures. To investigate the key interactions in the dynamic IDP α-synuclein (αS) at the amino acid level, we conducted single-molecule fluorescence resonance energy transfer (smFRET) experiments and coarse-grained molecular dynamics (CG-MD) simulations. We find excellent agreement between experiments and simulations. Our results show that a physiological salt solution is a good solvent for αS and that the protein is highly dynamic throughout its entire chain, with local intra- and inter-regional interactions leading to deviations from global scaling. Specifically, we observe expansion in the C-terminal region, compaction in the NAC region, and a slightly smaller distance between the C- and N-termini than expected. Our simulations indicate that the compaction in the NAC region results from hydrophobic aliphatic contacts, mostly between valine and alanine residues, and cation-π interactions between lysine and tyrosine. In addition, hydrogen bonds also seem to contribute to the compaction of the NAC region. The expansion of the C-terminal region is due to intraregional electrostatic repulsion and increased chain stiffness from several prolines. Overall, our study demonstrates the effectiveness of combining smFRET experiments with CG-MD simulations to investigate the key interactions in highly dynamic IDPs at the amino acid level.

High-throughput bioamphiphile production by ethyl methane sulphonate induced mutant of hydrocarbonoclastic Enterobacter xiangfangensis STP-3: In depth structural elucidation and application to petroleum refinery oil sludge bioremediation

The environmental release of noxious petroleum hydrocarbons (PHCs) from the petroleum refining industries is an intractable global challenge. Indigenous PHCs degrading microbes produce insufficient yield of amphiphilic biomolecules with trivial efficiency makes the bioremediation process ineffective. In this concern, the present study is focused on the production of high yield multi-functional amphiphilic biomolecule through the genetic modification of Enterobacter xiangfangensis STP-3 strain using Ethyl methane sulphonate (EMS) induced mutagenesis. Mutant M9E.xiangfangensis showed 2.32-fold increased yield of bioamphiphile than wild-type strain. Novel bioamphiphile produced by M9E.xiangfangensis exhibited improved surface and emulsification activities which ensure the maximum degradation of petroleum oil sludge (POS) by 86% than wild-type (72%). SARA, FT-IR, and GC-MS analyses confirmed the expedited degradation of POS and ICP-MS analysis indicated the enhanced removal of heavy metals in connection with the ample production of functionally improved bioamphiphile. FT-IR NMR, MALDI-TOF, GC-MS and LC-MS/MS analyses portrayed the lipoprotein nature of bioamphiphile comprising pentameric fatty acid moiety conjugated with the catalytic esterase moiety. Further, homology modelling and molecular docking revealed the stronger interaction of hydrophobic amino acids, leucine and isoleucine with the PHCs in the case of wild-type esterase moiety, whereas in the mutant, aromatic amino acids were majorly interacted with the long chain and branched chain alkanes, thereby exhibited better efficiency. This is the first report on the adoption of EMS induced mutagenesis strategy to ameliorate the amphiphilic biomolecules for their sustainable applications in diverse biotechnological, environmental and industrial arenas.

Usefulness of Docking and Molecular Dynamics in Selecting Tumor Neoantigens to Design Personalized Cancer Vaccines: A Proof of Concept.

Personalized cancer vaccines based on neoantigens are a new and promising treatment for cancer; however, there are still multiple unresolved challenges to using this type of immunotherapy. Among these, the effective identification of immunogenic neoantigens stands out, since the in silico tools used generate a significant portion of false positives. Inclusion of molecular simulation techniques can refine the results these tools produce. In this work, we explored docking and molecular dynamics to study the association between the stability of peptide-HLA complexes and their immunogenicity, using as a proof of concept two HLA-A2-restricted neoantigens that were already evaluated in vitro. The results obtained were in accordance with the in vitro immunogenicity, since the immunogenic neoantigen ASTN1 remained bound at both ends to the HLA-A2 molecule. Additionally, molecular dynamic simulation suggests that position 1 of the peptide has a more relevant role in stabilizing the N-terminus than previously proposed. Likewise, the mutations may have a "delocalized" effect on the peptide-HLA interaction, which means that the mutated amino acid influences the intensity of the interactions of distant amino acids of the peptide with the HLA. These findings allow us to propose the inclusion of molecular simulation techniques to improve the identification of neoantigens for cancer vaccines.

Artificial intelligence-assisted analysis reveals amino acid effects and interactions on Limosilactobacillus fermentum growth.

To understand the growth of lactic acid bacteria (LAB), Limosilactobacillus fermentum, in response to medium compositions, a deep neural network (DNN) was designed using amino acids (AAs) as explanatory variables and LAB growth as the objective variable. Sixty-four different patterns of free AAs were set using an orthogonal array. The best DNN model had high accuracy with low mean square errors and predicted that Asp would affect LAB growth. Bayesian optimization (BO) using this model recommended an optimal growth media comprising maximum amounts of Asn, Asp, Lys, Thr, and Tyr and minimum amounts of Gln, Pro, and Ser. Furthermore, this proposed media was empirically validated to promote LAB growth. The absence of Gln, Ser, and Pro indicates that the different growth trends among the DNN-BO-optimized media were likely caused by the interactions among the AAs and the other components.

A perception into binary and ternary copper (II) complexes: synthesis, characterization, DFT modeling, antimicrobial activity, protein binding screen, and amino acid interaction

Ensuring healthy lives and promoting well-being for all at all ages is the third goal of the sustainable development plan, so it was necessary to identify the most important problems that threaten health in our world. The World Health Organization declared that antibiotic resistance is one of the uppermost global public health threats facing humanity and searching for new antibiotics is slow. This problem can be approached by improving available drugs to combat various bacterial threats. To circumvent bacterial resistance, three copper(II) complexes based on the pefloxacin drug were prepared and characterized using analytical, spectroscopic, and thermal techniques. The resulting data suggested the formation of one octahedral binary and two distorted square pyramidal ternary complexes. Fluorescence spectra results revealed the formation of a turn-on fluorophore for amino acid detection. Computational calculations investigated quantum and reactivity parameters. Molecular electrostatic potential profiles and noncovalent bond interaction-reduced density gradient analysis indicated the active sites on the complex surface. The complexes were subjected to six microbial species, where the octahedral binary complex provoked its antimicrobial potency in comparison with ternary complexes. The enhanced antimicrobial activity against gram-negative bacterium E-coli compared to gentamicin was exhibited by the three complexes. Docking simulation was performed based on the crystal structure of E. coli and S. pneumoniae receptors using 5I2D and 6O15 codes. The binary complex exhibited a potent fitness score with 5I2D (TBE = − 107 kcal/mol) while ternary complexes displayed the highest docked score of fitness with 6O15.

Novel thioxoimidazolidinone derivatives as dual EGFR and CDK2 inhibitors: Design, synthesis, anticancer evaluation with in silico study

Fifteen thioxoimidazolidinone derivatives were designed as dual EGFR and CDK2 inhibitors and synthesized following Claisen and Knoevenagel condensation. Derivative 12 showed the best EGFR and CDK2 IC50 giving 0.098 μM and 0.087 μM, respectively, followed by 13 with IC50 0.108 μM and 0.144 μM, respectively. Both derivatives showed better cancerous cell line growth inhibition than erlotinib over HCT-116, MCF-7, and HepG-2. Furthermore, the colorectal HCT-116 was the most responsive to treatment with IC50 of 1.87 μM and 2.70 μM for 12 and 13, respectively in comparison to 15.40 μM of erlotinib. Moreover, the molecular docking simulation of 12 and 13 explained their astonishing kinase inhibition at the molecular level, where both exhibited better EGFR binding energy than its co-crystallized ligand consolidated with the crucial amino acid interactions. Similarly, derivative 12 showed comparable binding energy to CDK2 to its co-crystallized ligand and demonstrated the characteristic interactions with CDK2 binding site and gatekeeper residues.

Exploring therapeutic activity of Standard extract of Bacopa monnieri (Brahmi): Indian Ayurvedic Herb

AbstractBackgroundAlzheimer’s disease (AD) is one of the world’s most debilitating diseases, affecting over 24 million people worldwide. Many synthetic medications developed for Alzheimer’s disease were ineffective in treating the disease, however, they were able to control the symptoms to some extent. As a result, effective bioactive chemicals are in high demand. Bacopa monnieri is an Indian herb that has been used to treat a variety of neurological disorders, according to artifacts and literature (NDDs). We want to find bioactive molecules that target distinct indicators involved in the Alzheimer’s hypothesis. The goal of this study was to learn more about Bacopa monnieri’s potential to combat various AD targets.MethodThe research involved the in‐silico approach by performing docking studies of all bioactive compounds of Bacopa monnieri and target AChE, BuChE, MAO‐A, BACE1, NMDA & APOE. All the ligands of extract were selected from the database and the protein along with ligand were prepared and docking was performed using the Glide module of Schrodinger. Further, the free energy of the complex was calculated using the MM‐GBSA of the prime module. ADME and Bioactivity scores were also analyzed for further understanding.ResultThe results demonstrate free binding and free complex energies for all the phytocompounds of Bacopa monnieri. MAO‐A, AChE, BuChE, and NMDA have shown greater binding affinities than the respective controls. The good scoring compounds were further checked for their Free Energy calculations to ensure their stability. The ADMET properties and bioactivity scores revealed the best stability of the compounds in the human system.ConclusionThe results of the study indicated that the formulations of Bacopa monnieri can be one of the potent therapeutic components against AChE, BuChE, MAO‐A, BACE1, NMDA & APOE, based on the docking scores, free energies, amino acid interactions, ADME, bioactivity, and toxicity. Amongst all, key compounds that showed good binding energies compared to controls for all the targets were L‐Arabinose, DL‐Aspartic acid, L‐Ascorbic acid, DL‐Alanine, and 2,3‐dimethylaniline. Henceforth, it is an effective therapeutic candidate for AD.

Alanine Substitution to Determine the Effect of LR5 and YR6 Rice Peptide Structure on Antioxidant and Anti-Inflammatory Activity.

The relationship between the structure of peptides LR5 (LHKFR) and YR6 (YGLYPR) and their antioxidant and anti-inflammatory activity remains unclear. Herein, leucine, tyrosine, proline, and phenylalanine at different positions in the peptides were replaced by Alanine (Ala), and two new pentapeptides (AR5 and LAR5) and four hexapeptides (AGR6, YAR6, YLR6, and YGR6) were obtained. The effect of Ala replacement on the hydrophobicity, cytotoxicity, NO inhibition rate, and active oxygen radical scavenging ability of these peptides and their antioxidant and anti-inflammatory abilities were investigated. The results indicated that the hydrophobicity of the peptides was associated with their amino acid composition and their specific sequence. However, hydrophobicity had no significant effect on cytotoxicity. Ala replacement was shown to enhance hydrophobicity and consequently increased the antioxidant and anti-inflammatory activity of the peptides. The molecular docking studies indicated that the amino acid interactions of the peptide with the Keap1 protein influenced the hydrophobicity and thus affected the antioxidant activity of the peptide.

New Hypothesis Insight of Structural Properties on Four Tau Peptide Fragments in Alzheimer's Disease: Origin from the Histidine Behaviors.

During protein folding and misfolding, structural properties and aggregation tendency can be significantly influenced by histidine behaviors (tautomeric behaviors and protonation behaviors). The original reasons were derived from the net charge changes and the various N/N-H orientation on imidazole rings. In the current study, total 18 independent REMD simulations were performed to investigate the histidine behaviors on four Tau peptide fragments (MBD, including R1, R2, R3, and R4 fragments). We found that, compared to R1, R2, R3 except (εδ), and R4 systems with flexible structural features, only R3(εδ) has dominating conformational structure (possibility of 81.3%) with three β-strand structures in parallel β-sheet structures at I4-K6and I24-H26, as well as antiparallel β-sheet structure at G19-L21. Importantly, the H25 and H26 residues (in R3(εδ) system) are directly involved in the sheet structure formations and strong H-bonded interactions (possibility range of 31.3%-44.7%). Furthermore, the donors and acceptors analysis confirmed that only R3(εδ) shows faraway amino acids interaction features in both H25 and H26 residues, and such cooperation effects of two histidine residues contribute to current structural features. The current study will be helpful to further enrichment of the histidine behavior hypothesis, it provides new insight for understanding protein folding and misfolding.

Guiding protein design choices by per-residue energy breakdown analysis with an interactive web application.

Recent developments in machine learning have greatly facilitated the design of proteins with improved properties. However, accurately assessing the contributions of an individual or multiple amino acid mutations to overall protein stability to select the most promising mutants remains a challenge. Knowing the specific types of amino acid interactions that improve energetic stability is crucial for finding favorable combinations of mutations and deciding which mutants to test experimentally. In this work, we present an interactive workflow for assessing the energetic contributions of single and multi-mutant designs of proteins. The energy breakdown guided protein design (ENDURE) workflow includes several key algorithms, including per-residue energy analysis and the sum of interaction energies calculations, which are performed using the Rosetta energy function, as well as a residue depth analysis, which enables tracking the energetic contributions of mutations occurring in different spatial layers of the protein structure. ENDURE is available as a web application that integrates easy-to-read summary reports and interactive visualizations of the automated energy calculations and helps users selecting protein mutants for further experimental characterization. We demonstrate the effectiveness of the tool in identifying the mutations in a designed polyethylene terephthalate (PET)-degrading enzyme that add up to an improved thermodynamic stability. We expect that ENDURE can be a valuable resource for researchers and practitioners working in the field of protein design and optimization. ENDURE is freely available for academic use at: http://endure.kuenzelab.org.

Fast and accurate protein structure search with Foldseek

As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the structure of a query protein against a database by describing tertiary amino acid interactions within proteins as sequences over a structural alphabet. Foldseek decreases computation times by four to five orders of magnitude with 86%, 88% and 133% of the sensitivities of Dali, TM-align and CE, respectively.

Selective PPAR-Delta/PPAR-Gamma Activation Improves Cognition in a Model of Alzheimer's Disease.

Background: The continuously increasing association of Alzheimer's disease (AD) with increased mortality rates indicates an unmet medical need and the critical need for establishing novel molecular targets for therapeutic potential. Agonists for peroxisomal proliferator activating receptors (PPAR) are known to regulate energy in the body and have shown positive effects against Alzheimer's disease. There are three members of this class (delta, gamma, and alpha), with PPAR-gamma being the most studied, as these pharmaceutical agonists offer promise for AD because they reduce amyloid beta and tau pathologies, display anti-inflammatory properties, and improve cognition. However, they display poor brain bioavailability and are associated with several adverse side effects on human health, thus limiting their clinical application. Methods: We have developed a novel series of PPAR-delta and PPAR-gamma agonists in silico with AU9 as our lead compound that displays selective amino acid interactions focused upon avoiding the Tyr-473 epitope in the PPAR-gamma AF2 ligand binding domain. Results: This design helps to avoid the unwanted side effects of current PPAR-gamma agonists and improve behavioral deficits and synaptic plasticity while reducing amyloid-beta levels and inflammation in 3xTgAD animals. Conclusions: Our innovative in silico design of PPAR-delta/gamma agonists may offer new perspectives for this class of agonists for AD.

In Silico Prediction of Antidiabetic Activity of Phytoconstituents of Pterocarpus Marsupium Targeting α-Amylase Enzyme

ABSTRACT: Background Diabetes is characterized by a metabolic imbalance of blood sugar levels. α-amylase enzyme hydrolyzed starch into glucose units. Current therapy has significant side effects. Current investigation of in silico antidiabetic evaluation of phytoconstituents of Pterocarpus marsupium targeting α-amylase. Methods In silico studies were investigated to determine the binding affinity of phytoconstituents of Pterocarpus marsupium in additional with the crystal structure of α-amylase (PDB ID: 3BC9) with help of Pyrx in autodock vina software. Further, investigate the amino acid interaction residue and impacts on the inhibitory potential of the active phytoconstituents. Additionally, the pharmacokinetics and SwissADME and pkCSM were used as online servers for the toxic effects research. Further, studied the pocket region of amino acid for the binding of phytoconstituents using the Ramachandran plot. Result Molecular docking results proposed that pterostilbenes and liquirtigenin (-8.1 kcal/mol) had best docked against α-amylase as related to native ligand (-5.6 kcal/mol) and metformin (-5.3 kcal/mol). The active phytoconstituent has actively participated in interaction with the amino acid residue leads to blockage of α-amylase activity. Furthermore, the pharmacokinetic and In ADMET investigations, the phytoconstituents toxicological values are within allowable ranges. Conclusion The most promising outcome was revealed by the phytoconstituents of Pterocarpus marsupium that bind to α -amylase. However, it encourages the traditional practice of Pterocarpus marsupium and delivers vital information in drug development and clinical treatment. It promotes traditional approach of Pterocarpus marsupium and provides crucial knowledge for medical research and therapeutic care.

Exploring Oxidoreductases from Extremophiles for Biosynthesis in a Non-Aqueous System.

Organic solvent tolerant oxidoreductases are significant for both scientific research and biomanufacturing. However, it is really challenging to obtain oxidoreductases due to the shortages of natural resources and the difficulty to obtained it via protein modification. This review summarizes the recent advances in gene mining and structure-functional study of oxidoreductases from extremophiles for non-aqueous reaction systems. First, new strategies combining genome mining with bioinformatics provide new insights to the discovery and identification of novel extreme oxidoreductases. Second, analysis from the perspectives of amino acid interaction networks explain the organic solvent tolerant mechanism, which regulate the discrete structure-functional properties of extreme oxidoreductases. Third, further study by conservation and co-evolution analysis of extreme oxidoreductases provides new perspectives and strategies for designing robust enzymes for an organic media reaction system. Furthermore, the challenges and opportunities in designing biocatalysis non-aqueous systems are highlighted.

Effect of ethylene gas and Tryptophan amino acid in two oat varieties under soil stress conditions

A field experiment was conducted at the Research Station, Agriculture Faculty, Al-Muthanna University. The investigation was applied using the split-plot design, according to RCBD, with three replicates, varieties occupied the main plots, amino acid tryptophan occupied the sub-plots, and ethylene levels occupied the sub-sub-plot. The results showed that Shifaa Variety was distinguished in the harvest index. Results showed its distinction in the characteristic of the Panicle number. The interaction between the varieties and the amino acids showed increased grain yield percentage and the Panicle numbers when the amino acid was added. The exchange of cultivars with ethylene showed a decrease in plant height at 250 ppm and an increase in the Panicle numbers, the tiller numbers and the number of grains Panicle -1. As for the interaction of amino acid with ethylene, the treatment of adding acid and concentration of 250 ppm was superior with increasing some traits, including the number of grains Panicle -1, grain yield tons ha-1 and biological yield. While in the triple interaction, the treatment of (oat 11 × amino acid × the addition of Ethylene 250 ppm) was superior on some traits, including the increase in, the Panicle numbers and 1000 grain weight. Keywords: ethylene gas, Tryptophan amino acid, oat, soil stress conditions

Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity

The objective of this study was to obtain co-amorphous systems of poorly soluble sinapic acid using amino acids as co-formers. In order to assess the probability of the interaction of amino acids, namely, arginine, histidine, lysine, tryptophan, and proline, selected as co-formers in the amorphization of sinapic acid, in silico studies were carried out. Sinapic acid systems with amino acids in a molar ratio of 1:1 and 1:2 were obtained using ball milling, solvent evaporation, and freeze drying techniques. X-ray powder diffraction results confirmed the loss of crystallinity of sinapic acid and lysine, regardless of the amorphization technique used, while remaining co-formers produced mixed results. Fourier-transform infrared spectroscopy analyses revealed that the co-amorphous sinapic acid systems were stabilized through the creation of intermolecular interactions, particularly hydrogen bonds, and the potential formation of salt. Lysine was selected as the most appropriate co-former to obtain co-amorphous systems of sinapic acid, which inhibited the recrystallization of sinapic acid for a period of six weeks in 30 °C and 50 °C. Obtained co-amorphous systems demonstrated an enhancement in dissolution rate over pure sinapic acid. A solubility study revealed a 12.9-fold improvement in sinapic acid solubility after introducing it into the co-amorphous systems. Moreover, a 2.2-fold and 1.3-fold improvement in antioxidant activity of sinapic acid was observed with respect to the ability to neutralize the 2,2-diphenyl-1-picrylhydrazyl radical and to reduce copper ions, respectively.

Synthesis, Antidiabetic Evaluation and Molecular Docking Studies of Thiazolidine-2,4-Dione Analogues

Abstract: Introduction: Diabetes Mellitus is a disorder of metabolism described by high glucose levels. The disorder kills a larger number of individuals consistently than of malignant growth and AIDS combined. Presently available drugs have several drawbacks forcing to withdraw from treatment. The potent side effect i.e., hepatotoxicity and cardiovascular toxicity limits the use of thiazolidine-2,4-dione derivative as safe drugs. Our aim is towards the development of synthetic compounds as potential antidiabetic agents, particularly preparation and screening of new analogues of thiazolidine-2,4-dione (TZD) which are well established as oral insulin sensitizing agents that improve insulin resistance and are agonists of Peroxisome Proliferator Activated Receptor–γ (PPAR-γ). Materials and Methods: Proper substitution at C-5 position of thiazolidine-2,4-dione could produce better and potential antidiabetics with improved pharmacological properties, including toxicity. Our aim of this research work is towards this. Results: A series of C-5 substituted thiazolidine-2,4-dione analogues were synthesized. Structures of these new analogues were confirmed by IR, 1H-NMR and MASS spectroscopy. Among the synthesized compounds, three compounds: 5-(2-pyridinylbenzylidene) thiazolidine-2,4-dione, 5-(3,4-dimethoxybenzylidene) thiazolidine-2,4-dione and 5-(2,3,4-trifluorobenzylidene) thiazolidine-2,4-dione showed significant antidiabetic activity in streptozotocin induced diabetic mice comparable with Pioglitazone drug. The molecular docking studies of these compounds performed using protein target showed amino acid interactions with Leu270, Gln283 and Arg288 similar with that of Rosiglitazone and Pioglitazone. The compounds did not show any toxic effect in mice even at 2000 mg/kg of dose. Therefore, synthesis of modified and better thiazolidine-2,4-dione containing drugs other than the currently available drugs is of importance in antidiabetic drug research. Keywords: Thiazolidine-2,4-dione, Molecular docking, Antidiabetic evaluation, Swiss albino mice.

Phytocompound inhibitors of caspase 3 as beta-cell apoptosis treatment development option: An In-silico approach

The prevalence of Diabetes mellitus (DM) is continuously rising worldwide. Among its types, type I is characterized by the destruction of beta cells triggered by various mechanisms, including the activation of Caspase 3. Studies have demonstrated the crucial role of Caspase 3 in initiating the apoptosis of beta cells in DM. Our research aims to identify possible phytocompounds inhibitors of Caspase 3 using computational approach. We obtained 3D structures of Caspase 3 and 6511 phytocompounds from the Protein Data Bank and the African Natural Products Database, respectively. The phytocompounds were assessed for druglikeness properties, topological polar surface area, and preliminary toxicity using DataWarrior. The phytocompounds were subjected to molecular docking simulation (MDS) at Caspase 3 active site using AutoDock-Vina. The frontrunner phytocompounds obtained from the MDS were subjected to protease inhibition prediction on Molinspiration. The pharmacokinetics of the phytocompounds were assessed on SwissADME. The in-depth computational toxicity profile of the phytocompounds was evaluated on the pkCSM web. The binding interactions of the phytocompounds with Caspase 3 were assessed with Discovery Studio Visualizer and Maestro. Seventeen phytocompounds were found to have no violation of Lipinski's rule and had no toxicity based on the preliminary assessment, have better binding affinity and protease inhibitory prediction scores than the references, have optimistic bioactivity radar prediction and similar amino acids interaction, in comparison with the references. Further studies, which include in-vitro and in-vivo studies, will be carried out to validate the results of this study.