title: Synthesis and antibacterial activity of novel 4-bromo-1H-indazole derivatives as FtsZ inhibitors.
abstract: A series of novel 4-bromo-1H-indazole derivatives as filamentous temperature-sensitive protein Z (FtsZ) inhibitors were designed, synthesized, and assayed for their in vitro antibacterial activity against various phenotypes of Gram-positive and Gram-negative bacteria and their cell division inhibitory activity. The results indicated that this series showed better antibacterial activity against Staphylococcus epidermidis and penicillin-susceptible Streptococcus pyogenes than the other tested strains. Among them, compounds 12 and 18 exhibited 256-fold and 256-fold more potent activity than 3-methoxybenzamide (3-MBA) against penicillin-resistant Staphylococcus aureus, and compound 18 showed 64-fold better activity than 3-MBA but 4-fold weaker activity than ciprofloxacin in the inhibition of S. aureus ATCC29213. Particularly, compound 9 presented the best activity (4 µg/mL) against S. pyogenes PS, being 32-fold, 32-fold, and 2-fold more active than 3-MBA, curcumin, and ciprofloxacin, respectively, but it was four times less active than oxacillin sodium. In addition, some synthesized compounds displayed moderate inhibition of cell division against S. aureus ATCC25923, Escherichia coli ATCC25922, and Pseudomonas aeruginosa ATCC27853, sharing a minimum cell division concentration of 128 µg/mL.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Mi
authors.initials: M
authors.lastname: Yan
authors.forename: Ruixin
authors.initials: R
authors.lastname: Ma
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D007191:Indazoles
keywords: Antibacterial evaluation; FtsZ inhibitors; Indazole derivatives; Resistant bacteria; Synthesis