Design and Synthesis of a Focused Library of Diamino Triazines as Potential Mycobacterium tuberculosis DHFR Inhibitors

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• 作者：Arundhati C. Lele ; Archana Raju ; Mihir P. Khambete ; M. K. Ray ; M. G. R. Rajan ; Manisha A. Arkile ; Nandadeep J. Jadhav ; Dhiman Sarkar ; Mariam S. Degani
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：November 12, 2015
• 年：2015
• 卷：6
• 期：11
• 页码：1140-1144
• 全文大小：310K
• ISSN：1948-5875

文摘

We report design of a series of 2,4-diamino triazines as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors. The synthesized compounds were evaluated against Mtb (H₃₇Rv and Dormant stage H₃₇Ra), their cytotoxicity was assessed (HepG2 and A549 cell lines), and selectivity toward Mtb was evaluated by testing against other bacterial strains. Some derivatives showed promising activity along with low cytotoxicity. The most potent compound in the whole cell assay (MIC 0.325 渭M against H₃₇Rv) showed selectivity in the enzyme assay and exhibited synergy with second line anti-TB agent p-amino salicylic acid. This study therefore provides promising molecules for further development as antituberculosis DHFR inhibitors.