1. Academic Validation
  2. Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors

Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors

  • Bioorg Med Chem. 2020 Nov 15;28(22):115776. doi: 10.1016/j.bmc.2020.115776.
Fumihito Ushiyama 1 Hideaki Amada 2 Yasuhiro Mihara 2 Tomoki Takeuchi 2 Nozomi Tanaka-Yamamoto 2 Masashi Mima 2 Masafumi Kamitani 2 Reiko Wada 2 Yunoshin Tamura 2 Mayumi Endo 2 Aiko Masuko 2 Iichiro Takata 2 Kosuke Hitaka 2 Hiroyuki Sugiyama 2 Norikazu Ohtake 2
Affiliations

Affiliations

  • 1 Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-Cho, Kita-Ku, Saitama 331-9530, Japan. Electronic address: f-ushiyama@taisho.co.jp.
  • 2 Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-Cho, Kita-Ku, Saitama 331-9530, Japan.
Abstract

The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chemical class of Antibacterial drug is eagerly desired. We aimed at creating novel Antibacterial agents against Bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC90 values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 μg/mL, respectively. Hence, TP0480066 can be regarded as a promising Antibacterial drug candidate of this chemical class.

Keywords

Antibacterial agent; Antimicrobial resistance; Bacterial type II topoisomerase; DNA gyrase; Topoisomerase IV.

Figures
Products