Virtual Screening of Novel 2-substituted -5-hydroxy-1- (2-methyl-3-morpholinopropyl)-1H-indole-3- carboxamide Derivatives for Estrogen Receptor alpha in AF-2 domain for effective Anticancer Treatment

S.N. Wagh; B.J. Warude; V.A. Chatpalliwar

Abstract

Present manuscript describes designing of novel 2-substituted -5-hydroxy-1-(2-methyl-3- morpholinopropyl)-1H-indole-3-carboxamide derivatives as specific ERα modulators, discuss the selection criteria for 1ERR, several interactions between the ligand and the amino acid residues that would probably elicit fruitful modulation of the receptor. Accordingly, a ligand was observed to yield Gscore of -10.016 which was found comparable with the standard ligand Raloxifene (-11.869). The present work has been designed to discover some novel 2-substituted -5-hydroxy-1-(2-methyl-3- morpholinopropyl)-1H-indole-3-carboxamide derivatives and their screening through molecular docking. This work involved designing novel 2-substituted-5-hydroxy-1-(2-methyl-3- morpholinopropyl)-1H-indole-3-carboxamide derivatives and their screening by docking studies to determine the binding interaction for the best-fit conformations in the binding site of the ERα receptor. Based on the results of docking studies, the selected ligands reveal the all-important functional groups of the ligands that interact with active amino acid residues in the targeted cavity. Which, if persist in molecules may elicit the desired response in vitro. Amongst the designed derivatives, ligands BC65, BC58, BC64, BC60, BC63 BC61, and BC77 have shown better binding energy comparable with standard, Raloxifene. The observed results lamented the presence of a substitution at C-2 position of indole scaffold, either a straight or branched with terminal atom containing non-bonding electrons (halide/-NH2). Accordingly, ligand BC65 carrying methylbenzene chain (GScore= -10.016), whereas BC58 carrying hydroxybenzene chain (GScore = -9.818), whereas BC64 carrying amino benzene chain (Gscore = -9.598) were found to interact suitably with the active amino acid residues in targeted cavity that are reported to be involved in interaction with the standard. From the present results, we conclude that designed derivatives have potential to modulate ERα receptor effectively which can be synthesized and tested for their effectivity, in vitro and in vivo against breast cancer.

Abstract

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