Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents

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• 作者：Chia-Yi Cheng ; Chun-Ping Chang ; Tsai-Ling Yang Lauderdale ; Guann-Yi Yu ; Jinq-Chyi Lee ; Yi-Wun Jhang ; Chien-Huang Wu ; Yi-Yu Ke ; Amit A. Sadani ; Ching-Fang Yeh ; I-Wen Huang ; Yi-Ping Kuo ; De-Jiun Tsai ; Teng-Kuang Yeh ; Chen-Tso Tseng ; Jen-Shin Song ; Yu-Wei Liu ; Lun K. Tsou ; Kak-Shan Shia
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：December 8, 2016
• 年：2016
• 卷：7
• 期：12
• 页码：1191-1196
• 全文大小：321K
• ISSN：1948-5875

文摘

Series of N-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N-substituted carbazoles as potential anti-MRSA agents.