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Updated: Apr 10, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Rational drug design, synthesis and biological evaluation of dihydrofolate reductase inhibitors as antituberculosis
Nilesh R Tawari1, Seema Bag1, Archana Raju1
1Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
Background:
A series of 2,4-diamino-s-triazines was designed, with potential for activity against Mycobacterium tuberculosis (Mtb) dihydrofolate reductase enzyme, on the basis of virtual screening results and structure-based drug design.
Results:
The compounds were evaluated against Mtb (H37Rv) and their cytotoxicity was assessed using VERO cell lines. Of particular note, two compounds were found to have the most promising antituberculosis activity (6b minimum inhibitory concentration: 1.76 μM and 6i minimum inhibitory concentration: 1.57 μM) along with low cytotoxicity (CC50: >300 μM). The enzyme assay results of these two indicated significant inhibition of Mtb dihydrofolate reductase along with selectivity. Selected derivatives were tested against dormant tubercle bacilli in vivo and ex vivo indicating potential inhibition.
Conclusion:
This study provides promising antituberculosis dihydrofolate reductase inhibitors that can act as potential leads for further development.
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