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

Article abstract of DOI:10.1021/acsmedchemlett.6b00289

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.

Full text of DOI:10.1021/acsmedchemlett.6b00289

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Letter
Bromomethylthioindole Inspired Carbazole
Hybrids as Promising Class of Anti-MRSA Agents
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, and Kak-Shan Shia
ACS Med. Chem. Lett., Just Accepted Manuscript • DOI: 10.1021/acsmedchemlett.6b00289 • Publication Date (Web): 21 Oct 2016
Downloaded from http://pubs.acs.org on October 23, 2016
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