Kaur, HSingh, LChibale, KSingh, K2024-06-172024-06-172019-10-18Kaur H, Singh L, Chibale K, Singh K. Structure elaboration of isoniazid: synthesis, in silico molecular docking and antimycobacterial activity of isoniazid-pyrimidine conjugates. Mol Divers. 2020 Nov;24(4):949-955. doi: 10.1007/s11030-019-10004-1.https://doi.org/10.1007/s11030-019-10004-1https://pubmed.ncbi.nlm.nih.gov/31691051https://hdl.handle.net/11288/596630Designing small molecule-based new drug candidates through structure modulation of the existing drugs has drawn considerable attention in view of inevitable emergence of resistance. A new series of isoniazid-pyrimidine conjugates were synthesized in good yields and evaluated for antitubercular activity against the H37Rv strain of Mycobacterium tuberculosis using the microplate Alamar Blue assay. Structure-anti-TB relationship profile revealed that conjugates 8a and 8c bearing a phenyl group at C-6 of pyrimidine scaffold were most active (MIC99 10 µM) and least cytotoxic members of the series. In silico docking of 8a in the active site of bovine lactoperoxidase as well as a cytochrome C peroxidase mutant N184R Y36A revealed favorable interactions similar to the heme enzyme catalase peroxidase (KatG) that activates isoniazid. This investigation suggests a rationale for further work on this promising series of antitubercular agents.enAttribution 3.0 United Stateshttp://creativecommons.org/licenses/by/3.0/us/ADMEConjugatesDrug resistanceIsoniazidMolecular dockingPyrimidineArticleMolecular Diversity