Open AccessOPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor
Author(s) -
Norimitsu Hariguchi,
Xiuhao Chen,
Yohei Hayashi,
Yoshikazu Kawano,
M̄. Fujiwara,
Miki Matsuba,
Hiroshi Shimizu,
Yoshio Ohba,
Ippei Nakamura,
Ryuki Kitamoto,
Toshio Shinohara,
Yukitaka Uematsu,
Shunpei Ishikawa,
Motohiro Itotani,
Yoshikazu Haraguchi,
Isao Takemura,
Makoto Matsumoto
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02020-19
Subject(s) - bedaquiline , moxifloxacin , pharmacology , mycobacterium tuberculosis , tuberculosis , linezolid , medicine , levofloxacin , microbiology and biotechnology , antibiotics , biology , bacteria , genetics , pathology , vancomycin , staphylococcus aureus
There is an urgent need for new, potent antituberculosis (anti-TB) drugs with novel mechanisms of action that can be included in new regimens to shorten the treatment period for TB. After screening a library of carbostyrils, we optimized 3,4-dihydrocarbostyril derivatives and identified OPC-167832 as having potent antituberculosis activity. The MICs of the compound for Mycobacterium tuberculosis ranged from 0.00024 to 0.002 μg/ml. It had bactericidal activity against both growing and intracellular bacilli, and the frequency of spontaneous resistance for M. tuberculosis H37Rv was less than 1.