MOLECULAR MODELING STUDIES OF BENZIMIDAZOLYL-CHALCONES AS ANTILEISHMANIAL AGENTS USING QSAR, DOCKING, ADME AND MOLECULAR DYNAMICS STUDIES

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.