Literature

Abstract

Bacterial RNA polymerase (RNAP) is essential for transcription and is an antibacterial target for small molecule inhibitors. The binding region of myxopyronin B (MyxB), a bacterial RNAP inhibitor, offers the possibility of new inhibitor design. The molecular design program SPROUT has been used in conjunction with the X-ray cocrystal structure of Thermus thermophilus RNAP with MyxB to design novel inhibitors based on a substituted pyridyl-benzamide scaffold. A series of molecules, with molecular masses <350 Da, have been prepared using a simple synthetic approach. A number of these compounds inhibited Escherichia coli RNAP.

DOI： 10.1021/ml200087m

Structure-Based Ligand Design of Novel Bacterial RNA Polymerase Inhibitors

ACS Medicinal Chemistry Letters 2011.0

Novel small molecule inhibitors targeting the “switch region” of bacterial RNAP: Structure-based optimization of a virtual screening hit

European Journal of Medicinal Chemistry 2013.0

Design, synthesis and biological evaluation of novel hybrids of N-aryl pyrrothine-base α-pyrone as bacterial RNA polymerase inhibitors

Bioorganic & Medicinal Chemistry Letters 2020.0

Syntheses of novel myxopyronin B analogs as potential inhibitors of bacterial RNA polymerase

Bioorganic & Medicinal Chemistry Letters 2007.0

Novel Hybrid-Type Antimicrobial Agents Targeting the Switch Region of Bacterial RNA Polymerase

ACS Medicinal Chemistry Letters 2013.0

Discovery of Novel Bacterial RNA Polymerase Inhibitors: Pharmacophore-Based Virtual Screening and Hit Optimization