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Novel hybrid-type antimicrobial agents targeting the switch region of bacterial RNA polymerase.

ABSTRACT: The bacterial RNA polymerase (RNAP) is an ideal target for the development of antimicrobial agents against drug-resistant bacteria. Especially, the switch region within RNAP has been considered as an attractive binding site for drug discovery. Here, we designed and synthesized a series of novel hybrid-type inhibitors of bacterial RNAP. The antimicrobial activities were evaluated using a paper disk diffusion assay, and selected derivatives were tested to determine their MIC values. The hybrid-type antimicrobial agent 29 showed inhibitory activity against Escherichia coli RNAP. The molecular docking study suggested that the RNAP switch region would be the binding site of 29.

SUBMITTER: Yakushiji F

PROVIDER: S-EPMC4027222 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Novel hybrid-type antimicrobial agents targeting the switch region of bacterial RNA polymerase.

Yakushiji Fumika F Miyamoto Yuko Y Kunoh Yuki Y Okamoto Reiko R Nakaminami Hidemasa H Yamazaki Yuri Y Noguchi Norihisa N Hayashi Yoshio Y

ACS medicinal chemistry letters 20130111 2

The bacterial RNA polymerase (RNAP) is an ideal target for the development of antimicrobial agents against drug-resistant bacteria. Especially, the switch region within RNAP has been considered as an attractive binding site for drug discovery. Here, we designed and synthesized a series of novel hybrid-type inhibitors of bacterial RNAP. The antimicrobial activities were evaluated using a paper disk diffusion assay, and selected derivatives were tested to determine their MIC values. The hybrid-typ ...[more]

PMID: 24900654

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