Design and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors
| Title | Design and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Lele, AC, Raju, A, Khambete, MP, Ray, MK, Rajan, MGR, Arkile, MA, Jadhav, NJ, Sarkar, D, Degani, MS |
| Journal | ACS Medicinal Chemistry Letters |
| Volume | 6 |
| Issue | 11 |
| Pagination | 1140-1144 |
| Date Published | NOV |
| ISSN | 1948-5875 |
| Keywords | Diamino 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. |
| DOI | 10.1021/acsmedchemlett.5b00367 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 3.355 |
Divison category:
Organic Chemistry