title: 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.
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Fumika
authors.initials: F
authors.lastname: Yakushiji
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kunoh
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Okamoto
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Nakaminami
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Noguchi
authors.affiliation: Departments of Medicinal Chemistry and Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
keywords: antimicrobial agent; bacterial RNA polymerase; bacterial RNA polymerase inhibitor; hybrid; switch region