Design and Synthesis of Diaminotriazines as Anti-Tuberculosis DHFR Inhibitors
Arundhati C Lele, Archana Raju, M.K. Ray, M.G.R. Rajan and Mariam S Degani
DOI : 10.3844/crddsp.2014.45.50
Current Research in Drug Discovery
Volume 1, Issue 2
A series of novel 2,4 diamino-s-triazine was designed as potential Mycobacterium tuberculosis (Mtb) Dihydro folate reductase inhibitors. The synthesized compounds were evaluated in whole cells by employing Resazurin Microtitre Plate Assay (REMA) against Mtb H37Rv, using known DHFR inhibitors Methotrexate and Trimethoprim as standard drugs. The most active compound in the whole cell assay was selected for DHFR enzyme assay against the pathogen and human enzymes. The enzyme assay results revealed that this compound is a selective pathogenic DHFR inhibitor, with 13 fold more selectivity than Methotrexate. Thus, these derivatives have provided promising selective Hits/Leads as MTb DHFR inhibitors and can provide valuable information for further design of potent anti-TB drugs.
© 2014 Arundhati C Lele, Archana Raju, M.K. Ray, M.G.R. Rajan and Mariam S Degani. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.