Exploration of new and potent lead molecules against CAAX prenyl protease I of Leishmania donovani through Pharmacophore based virtual screening approach.

This study mainly focuses on developing new and potent inhibitors against CAXX prenyl protease I of Leishmania donovani. MATERIALS AND METHODS: Pharmacophore based virtual screening was carried out using derivatives of bi-substrate analog farnesyl transferase inhibitors reported against CAAX prenyl proteases I. On the basis of ligand based pharmacophore model we have obtained 5 point pharmacophore AAADR with three hydrogen bond acceptors (A), one hydrogen bond donor (D) and one aromatic ring. The newly identified hits through pharmacophore model were further docked into the active site of the modeled protein. To get further insights of protein ligand interaction we have performed induced fit docking followed by molecular dynamics simulations. The DFT analysis depicts the electronic structure properties of the compounds. These results can be useful for the development of novel and potent CAAX prenyl protease I inhibitors. RESULTS: Initially, we have obtained a large number of newly identified hits by screening four different databases further docked into the active site of the protein and 20 compounds were selected on the basis of docking score. Perhaps Induced fit docking was performed to infer protein ligand interaction in a dynamic state and top 5 compounds 7118044, 7806909, LEG12866807, 9208535, SYN 19867403 were found to have good protein ligand interactions with key amino acid residues such as Glu287, His290 and additional interaction like Ile197, Asn209 ...
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research