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

作者：Yakushiji Fumika^*; Miyamoto Yuko; Kunoh Yuki; Okamoto Reiko; Nakaminami Hidemasa; Yamazaki Yuri; Noguchi Norihisa; Hayashi Yoshio

来源：ACS Medicinal Chemistry Letters, 2013, 4(2): 220-224.

DOI：10.1021/ml300350p

• bacterial RNA polymerase
• switch region
• antimicrobial agent
• bacterial RNA polymerase inhibitor
• hybrid

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 coil RNAP. The molecular docking study suggested that the RNAP switch region would be the binding site of 29.

• 出版日期2013-2