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Structure-based ligand design of novel bacterial RNA polymerase inhibitors.

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.

SUBMITTER: McPhillie MJ

PROVIDER: S-EPMC4017976 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Structure-based ligand design of novel bacterial RNA polymerase inhibitors.

McPhillie Martin J MJ Trowbridge Rachel R Mariner Katherine R KR O'Neill Alex J AJ Johnson A Peter AP Chopra Ian I Fishwick Colin W G CW

ACS medicinal chemistry letters 20110729 10

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 ...[more]

PMID: 24900260

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