MOLECULAR MODELING STUDIES OF BENZIMIDAZOLYL-CHALCONES AS ANTILEISHMANIAL AGENTS USING QSAR, DOCKING, ADME AND MOLECULAR DYNAMICS STUDIES
نویسندگان
چکیده
Introduction: Present leishmaniasis treatment regimen has many limitations including severe adverse effects, toxicity, and Leishmania strains resistance. In the present study, objective is to perform QSAR, molecular docking ADME prediction studies on benzimidazolylchalcones in order select an antileishmanial drug candidate.Materials & methods: QSAR models were performed 12 with activities against promastigote of L. donovani. Binding free energy calculations using MM-GBSA assess affinity ligands for proteins. addition, three most active compounds (4a-c, IC50 <1-μM) docked protein phosphodiesterase B1 (PDB ID: 2JK6).Results Discussion: The optimum model squared correlation coefficient (R2) 0.983, leave-one-out (LOO) cross-validation (Q2CV) value 0.942. number descriptors involved acceptable (R2 - Q2CV = 0.041), which confirms model’s stability validates developed predictive power. Docking revealed that best compound 4c formed hydrogen bond SER 464, pi-cation contact LYS 61 hydrophobic interactions LEU 62, TYR 64 LEU72 site donovani B1. properties results showed all molecules have good pharmacokinetic properties.Conclusion: Finally, dynamics simulation at 30 ns stable 2JK6 protein. This study choice ortho-chlorinated derivative as lead developing new derivatives optimized properties.
منابع مشابه
Structure Optimization of Neuraminidase Inhibitors as Potential Anti-influenza (H1N1Inhibitors) Agents Using QSAR and Molecular Docking Studies
The urgent need of neuraminidase inhibitors (NI) has provided an impetus for understanding the structure requisite at molecular level. Our search for selective inhibitors of neuraminidase has led to the identification of pharmacophoric requirements at various positions around acyl thiourea pharmacophore. The main objective of present study is to develop selective NI, with least toxicity and dru...
متن کاملStructure Optimization of Neuraminidase Inhibitors as Potential Anti-influenza (H1N1Inhibitors) Agents Using QSAR and Molecular Docking Studies
The urgent need of neuraminidase inhibitors (NI) has provided an impetus for understanding the structure requisite at molecular level. Our search for selective inhibitors of neuraminidase has led to the identification of pharmacophoric requirements at various positions around acyl thiourea pharmacophore. The main objective of present study is to develop selective NI, with least toxicity and dru...
متن کاملMolecular docking studies on xanthohumol derivatives as novel anticancer agents
A set of Xanthohumol derivatives were selected and molecular docking studies of these compounds on thioredoxin reductase were conducted. Based on new structural patterns using in silico-screening study, new potent lead compounds were designed. The results due to validated docking protocols lead to find that Thr58, Gly57, Gly21, Asp334, Glu163, Ala130, IIe332, Val44 and Gly132 are the main a...
متن کاملQSAR, Docking and Molecular Dynamics Studies on the Piperidone-grafted Mono- and Bis-spiro-oxindole-hexahydropyrrolizines as Potent Butyrylcholinesterase Inhibitors
ABSTRACT: Quantitative structure-activity relationship (QSAR) study on the piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent butyrylcholinestrase (BuChE) inhibitors were carried out using statistical methods, molecular dynamics and molecular docking simulation. QSAR methodologies, including classification and regression tree (CART), multiple linear regression (MLR),...
متن کاملA comparative QSAR analysis, molecular docking and PLIF studies of some N-arylphenyl-2,2-dichloroacetamide analogues as anticancer agents
Dichloroacetate (DCA) is a simple and small anticancer drug that arouses the activity of the enzyme pyruvate dehydrogenase (PDH) through inhibition of the enzyme pyruvate dehydrogenase kinases (PDK1-4). DCA can selectively promote mitochondria-regulated apoptosis, depolarizing the hyperpolarized inner mitochondrial membrane potential to normal levels, inhibit tumor growth and reduce proliferati...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of applied pharmaceutical sciences and research
سال: 2022
ISSN: ['2581-5520']
DOI: https://doi.org/10.31069/japsr.v4i3.4