Abstract:

Benzylidene hydrazide is a highly active moiety against Leishmania donovani, and has become a core structure for the design of new antileishmanial agents. The 5-nitrothiophen-2-yl-benzylidene hydrazide derivative presents a potent IC50 value. With this background, it is attempted to discern the structural and physicochemical requirements for the inhibition of Leishmania donovani. The techniques of quantitative structure activity relationship and docking are valuable molecular modeling tools for drug design. In the present study, 3-DQSAR of some Leishmania donovani inhibitors was carried out using VLife MDS, while interaction studies were carried usind Schrodinger molecular modeling interface. The developed QSAR models showed q2 = 0.9849, pred_r2 = 0.6770 with kNN analysis by stepwise forward and backward method. Docking study revealed important interactions of designed compounds with the active binding site of Leishmania donovani. Designed compounds were synthesis and screened against Leishmania donovani. Three compounds exhibited IC50 values lower than standard drugs. Brief SAR analysis revealed that substitution is important to the activity.

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