Aminopurine derivatives as putative SopE inhibitors

作者：Ozbuyukkaya Gizem; Olmez Elif Ozkirimli; Ulgen Kutlu Ozergin^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, 29(1): 137-145.

DOI：10.3109/14756366.2012.759217

• GEF inhibitor
• induced fit docking
• molecular docking
• structure-based pharmacophore building
• virtual screening

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.

• 出版日期2014-2