Design, Synthesis, and Structure鈥揂ctivity Correlations of Novel Dibenzo[b,d]furan, Dibenzo[b,d]thiophene, and N-Methylcarbazole Clubbed 1,2,3-Triazoles as Potent Inh

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• 作者：Santhosh Reddy Patpi ; Lokesh Pulipati ; Perumal Yogeeswari ; Dharmarajan Sriram ; Nishant Jain ; Balasubramanian Sridhar ; Ramalinga Murthy ; Anjana Devi T ; Shasi Vardhan Kalivendi ; Srinivas Kantevari
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 26, 2012
• 年：2012
• 卷：55
• 期：8
• 页码：3911-3922
• 全文大小：485K
• 年卷期：v.55,no.8(April 26, 2012)
• ISSN：1520-4804

文摘

A molecular hybridization approach is an emerging structural modification tool to design new molecules with improved pharmacophoric properties. In this study, 1,2,3-triazole-based Mycobacterium tuberculosis inhibitors and synthetic and natural product-based tricyclic (carbazole, dibenzo[b,d]furan, and dibenzo[b,d]thiophene) antimycobacterial agents were integrated in one molecular platform to prepare various novel clubbed 1,2,3-triazole hybrids using click chemistry. Structure鈥揳ctivity correlations and in vitro activity against M. tuberculosis strain H37Rv of new analogues revealed the order: dibenzo[b,d]thiophene > dibenzo[b,d]furan > 9-methyl-9H-carbazole series. Two of the most potent M. tuberculosis inhibitors 13h and 13q with MIC = 0.78 渭g/mL (1.9 渭M) displayed a low cytotoxicity and high selectivity index (50鈥?55) against four different human cancer cell lines. These results together provided the potential importance of molecular hybridization and the development of triazole clubbed dibenzo[b,d]thiophene-based lead candidates to treat mycobacterial infections.