2. Academic Validation
  3. 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.
PMID: 33032189 DOI: 10.1016/j.bmc.2020.115776
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