Research Article Open Access

Design and Synthesis of Diaminotriazines as Anti-Tuberculosis DHFR Inhibitors

Arundhati C Lele1, Archana Raju1, M.K. Ray1, M.G.R. Rajan1 and Mariam S Degani1
  • 1 , India
Current Research in Drug Discovery
Volume 1 No. 2, 2014, 45-50

DOI: https://doi.org/10.3844/crddsp.2014.45.50

Submitted On: 6 November 2014
Published On: 26 January 2015

How to Cite: Lele, A. C., Raju, A., Ray, M., Rajan, M. & Degani, M. S. (2014). Design and Synthesis of Diaminotriazines as Anti-Tuberculosis DHFR Inhibitors. Current Research in Drug Discovery, 1(2), 45-50. https://doi.org/10.3844/crddsp.2014.45.50

Abstract

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.

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Keywords

  • Mycobacterium Tuberculosis
  • Dihydrofolate Reductase
  • Diamino Triazine
  • Enzyme Inhibition Assay