Abstract
The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridization approach is described. The newly synthesized compounds 6a–k were evaluated for their in vitro antitubercular activity against active and dormant Mtb H37Ra and anti-oxidant activity against DPPH radical scavenging. Molecular docking simulations for the antitubercular activity showed that the conjugates 6a–k bind in the pocket of the DprE1 enzyme. Most of the conjugates displayed good antitubercular activity against both the active and dormant Mtb H37Ra strain. The compound 6h displayed very good antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1.44 μg/mL. Most of the synthesized conjugates exhibit excellent anti-oxidant activity with an IC50 of less than the standard BHT. Compound 6b is the most active among all the conjugates with an IC50 value of 08.17 ± 0.11 μg/mL. The molecular docking study shows good agreement between the observed antitubercular activity and the binding affinity.
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Acknowledgements
One of the authors, A.B.D., is very grateful to the University Grants Commission, New Delhi, for the award of a research fellowship. The authors are also grateful to the Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad-431 004, India, for providing necessary laboratory facilities. The authors are also grateful to Schrodinger, Inc. for providing the Demo license of the Schrodinger Molecular Modeling Suite to perform the molecular modeling studies.
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Danne, A.B., Choudhari, A.S., Sarkar, D. et al. Synthesis and biological evaluation of novel triazole-biscoumarin conjugates as potential antitubercular and anti-oxidant agents. Res Chem Intermed 44, 6283–6310 (2018). https://doi.org/10.1007/s11164-018-3490-1
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DOI: https://doi.org/10.1007/s11164-018-3490-1