Aminopurine derivatives as putative SopE inhibitors

Abstract

Salmonella outer protein E, SopE, is a virulence factor that is secreted from gram-negative Salmonella enterica, which is pathogenic to humans and is responsible for gastroenteritis and typhoid fever. SopE targets the Rho GTPase family proteins of the host cell and manipulates them by mimicking GTPase regulatory protein guanine nucleotide exchange factor. The aim of this work is the investigation of novel inhibitors against SopE. Structure-based pharmacophore modeling was used to identify structural features that would be important for SopE recognition. Glide fragment library was used for four-point pharmacophore hypothesis development. Small-molecule database screening was performed based on a 3D similarity to the best pharmacophore hypothesis. Binding affinity of filtered database molecules to SopE was predicted quantitatively by molecular docking and scoring using Glide software. Top scoring hits were further analyzed and five molecules were proposed as potent and selective SopE inhibitors. Four out of five proposed molecules were found to be aminopurine derivatives.

Identification of an inhibitor of the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] by glide molecular docking

“…We have recently identified compounds that inhibit the activity of AAC(6’)-Ib using AutoDock Vina 40 but they did not show any activity in vivo 21 . In this work we describe the identification of an AAC(6’)-Ib inhibitor by in silico molecular docking using Glide 41, 42 , a software that has been used to identify compounds that bind active sites and inhibit enzymatic activity 43, 44 .…”

“…21 In this work we describe the identification of an AACIJ6′)-Ib inhibitor by in silico molecular docking using Glide, 41,42 a software that has been used to identify compounds that bind active sites and inhibit enzymatic activity. 43,44…”