Design, synthesis and antimycobacterial activity of new benzothiazinones inspired by rifampicin/rifapentine
Wang A, Lu Y, Lv K, Ma C, Xu S, Wang B, Wang A, Xia G, et al. (9 authors)
Bioorganic chemistry · 2020-07
Abstract
A series of novel benzothiazinone derivatives containing a N-((methylene)amino)piperazine moiety, inspired by rifampicin/rifapentine, were designed and synthesized. Seven compounds 1a and 1e-j show excellent in vitro activity against both drug-sensitive MTB strain H37Rv and drug-resistant clinical isolates (MIC: 1100->4000). Compound 1h displays good safety and pharmacokinetic profiles, suggesting its promising potential to be lead compound for future antitubercular drug discovery.
MeSH terms
- Vero Cells
- Animals
- Mice, Inbred BALB C
- Mice
- Mycobacterium tuberculosis
- Thiazines
- Rifampin
- Anti-Bacterial Agents
- Microbial Sensitivity Tests
- Administration, Oral
- Cell Proliferation
- Molecular Structure
- Structure-Activity Relationship
- Dose-Response Relationship, Drug
- Drug Design
- Chlorocebus aethiops