Design and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors

TitleDesign and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors
Publication TypeJournal Article
Year of Publication2015
AuthorsLele, AC, Raju, A, Khambete, MP, Ray, MK, Rajan, MGR, Arkile, MA, Jadhav, NJ, Sarkar, D, Degani, MS
JournalACS Medicinal Chemistry Letters
Volume6
Issue11
Pagination1140-1144
Date PublishedNOV
ISSN1948-5875
KeywordsDiamino triazine, dihydrofolate reductase, enzyme assay, molecular modeling, Mycobacterium tuberculosis, selectivity, synergy
Abstract

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 (H(37)Rv 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 mu M against H(37)Rv) 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.

DOI10.1021/acsmedchemlett.5b00367
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

3.355

Divison category: 
Organic Chemistry