Synthesis and on-target antibacterial activity of novel 3-elongated arylalkoxybenzamide derivatives as inhibitors of the bacterial cell division protein FtsZ

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 14; pp. 4076 - 4079
• Main Authors: Ma, Siti, Cong, Chao, Meng, Xiaohui, Cao, Shasha, Yang, Hongkun, Guo, Yuanyuan, Lu, Xueyi, Ma, Shutao
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.07.2013; Elsevier
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; antibacterial properties; Arylalkoxybenzamide; Bacillus subtilis; Bacillus subtilis - drug effects; bacteria; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - metabolism; Benzamides - chemical synthesis; Benzamides - chemistry; Benzamides - pharmacology; cell division; Cell division inhibition activity; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytoskeletal Proteins - antagonists & inhibitors; Cytoskeletal Proteins - metabolism; FtsZ inhibitors; Life Sciences & Biomedicine; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Staphylococcus aureus; Staphylococcus aureus - drug effects; Synthesis; FtsZ inhibitors; Antibacterial activity; Synthesis; Cell division inhibition activity; Arylalkoxybenzamide; SMALL-MOLECULE INHIBITORS; RESISTANT STAPHYLOCOCCUS-AUREUS; INSIGHTS
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.05.056

Novel 3-elongated arylalkoxybenzamide derivatives were designed, synthesized and evaluated for their cell division inhibitory activity and antibacterial activity. Among them, the subseries of 3-alkyloxybenzamide derivatives exhibited greatly improved on-target activity against Bacillus subtilis and Staphylococcus aureus, and remarkably increased antibacterial activity against B. subtilis ATCC9372, penicillin-susceptible S. aureus ATCC25923, methicillin-resistant S. aureus ATCC29213 (MRSA) and penicillin-resistant S. aureus PR compared with 3-methoxybenzamide. In contrast, the subseries of 3-phenoxyaklyloxybenzamide, 3-heteroarylalkyloxybenzamide and 3-heteroarylthioalkyloxybenzamide derivatives only showed a significant improvement in on-target activity and antibacterial activity against B. subtilis ATCC9372.