Molecular docking based screening of G6PS with 1, 5 Benzothiazepine derivates for a potential inhibitor

Abstract

Glucosamine-6-phosphate synthase (G6PS) (EC 2.6.1.16) is a known target for anti-bacterial and anti-fungal infections. Therefore, it is of interest to design potential inhibitors using 1, 5 benzo-thiazepine skeleton with appropriate modifications. We report the binding data for 20 derivatives of the skeleton molecule to G6PS having binding energy from-7.35 to-9.99 Kcal/mol with predicted IC50 value range of 4.11 to 47.68 nano-molar. It should be noted that this data should be further evaluated using in vitro and in vivo studies for safety, activity, efficacy and toxicity. Background: L-Glutamine: d-fructose-6-phosphate amido-transferase, also known as glucosamine-6-phosphate synthase (GlcN6P synthase) [1], Glucosamine-6-phosphate synthase (L-glutamine: D-fructose-6-phosphate amino-transferase (GlmS, 1 EC 2.6.1.16)) catalyzes the first step in hexos-amine biosynthesis, an important constituent of the peptido-glycan layer of bacterial cell walls and fungal cell wall chitin [2]. Purification, partial biochemical and dynamics characterization of glucosamine-6-phosphate synthase was reported by Gonzalez et al. [3] and Mouilleron et al. [4] and its ability to act as antifungal drug target has been evaluated using modeling and structure based drug design by Wojciechowski et al. [5], whereas its catalytic function was described by Durand et al. [6]. Role of GlcN6P synthase in bacteria, eukaryotic organisms, glucose metabolism related to diabetes, cancer, inflammation and ulcer has been reviewed elsewhere [7] and hence, its potential as an anti-fungal target is known.