Virtual screening and molecular docking of Anti-Antileishmanial for selected pharmacophore for visceral Leishmaniasis

Abstract

Objective: DNA amplification of Cysteine protease of Leishmania donovani and study the interaction of cysteine protease inhibitors, antileishmanial compounds with cysteine protease receptor in various computational programs. Materials and methods: Cysteine protease DNA of Leishmania donovani was amplified by PCR. The sequence of cysteine protease has been modeled and docked with suitable inhibitors by using various servers and computational tools. The model was designed, compared and validated by DOPE and Verify 3D scores. The model and the compound interaction were studied by LibDock and other programs. Results: Cysteine protease DNA of Leishmania donovani was successfully amplified by PCR. The structural modeling was done to achieve effective enzyme inhibition, inhibitors block the binding sites of that protein. Homology modeling of cysteine protease has been done and docked with suitable inhibitors by using various servers and computational tools. The model was designed, compared and validated by DOPE and Verify 3D scores by using DSv3.5. Licochalcone-a alone showed 37 LibDock conformations with 6 different poses, were suitably docked at the site 1 with hydrogen bond formation. The study would help to design the novel drugs in respect of resistant one for the treatment of harmful visceral Leishmaniasis. Conclusion: The molecular interaction of vinyl sulfones, hydrazide derivatives, antileishmanial drugs molecules and carbohydrazide derivatives have exhibited ideal molecular interaction with cathepsin B, a cysteine protease of L. donovani, amino acids such as Cys29, Hisl88 and Asn208 has been found to be active residues. Licochalcone-a and hydrazide derivative may become future antileishmanial compounds, which needs to be tested in in vitro and in vivo. Keywords: Cysteine Protease, Vinyl Sulfone, Hydrazide, Antileishmanial Drugs, Licochalcone, Visceral Leishmaniasis.