A 2-D QSAR Modeling, Molecular Docking Study and Design of 2-Arylbenzimidazole Derivatives as Novel Leishmania Inhibitors: A Molecular Dynamics Study

Leishmaniasis, a neglected tropical disease, affects a human population of over 12 million people, mainly in the tropics, and is caused by the leishmanial parasites transmitted by the female sand fly. The lack of vaccines to prevent leishmaniasis, and the limitations of existing therapies necessitated this study, which was focused on the computational design of some novel 2-arylbenzimidazole analogs while subjecting the same to molecular docking, pharmacokinetics, and Molecular Dynamic (MD) simulation to ascertain their drug-ability. The obtained QSAR model was validated as follows: R2</sup> = 0.8447, R2</sup>adj</sub> = 0.8095, Q2</sup>cv</sub> = 0.6799, and R2</sup>test</sub> = 0.7383. The predicted pIC50</sub> values of all newly designed compounds were higher than that of the lead compound (13</strong>). The newly designed analogs conformed to Lipinski's rule for oral bio-availability less 13m</strong>, and showed good ADMET properties, with 13j</strong> showing the highest Human Intestinal Absorption (HIA) of 93.64%. The MD simulation result demonstrated excellent stability associated with the binding of 13j</strong> onto 6K91's binding pocket with an estimated ∆G binding (MM/GBSA) of -50.4031 kcal/mol than that of 13_6K91 (∆G binding = -25.9665 kcal/mol). Therefore, 13j</strong> could be recommended as a potential drug molecule for treating leishmanial infections.