Version 1
: Received: 28 March 2023 / Approved: 29 March 2023 / Online: 29 March 2023 (04:21:45 CEST)
How to cite:
Sheikh, B.A.; Bhat, B.A.; Zareen, H.; Rizvi, M.A.; Ahmad, Z.; Alkhanani, M.; Almilaibary, A.; Alsagaby, S.A.; Mir, M.A. Antituberculosis Propensity of Synthetic Biscoumarin Derivatives: An In Silico and In Vitro Approach. Preprints2023, 2023030502. https://doi.org/10.20944/preprints202303.0502.v1
Sheikh, B.A.; Bhat, B.A.; Zareen, H.; Rizvi, M.A.; Ahmad, Z.; Alkhanani, M.; Almilaibary, A.; Alsagaby, S.A.; Mir, M.A. Antituberculosis Propensity of Synthetic Biscoumarin Derivatives: An In Silico and In Vitro Approach. Preprints 2023, 2023030502. https://doi.org/10.20944/preprints202303.0502.v1
Sheikh, B.A.; Bhat, B.A.; Zareen, H.; Rizvi, M.A.; Ahmad, Z.; Alkhanani, M.; Almilaibary, A.; Alsagaby, S.A.; Mir, M.A. Antituberculosis Propensity of Synthetic Biscoumarin Derivatives: An In Silico and In Vitro Approach. Preprints2023, 2023030502. https://doi.org/10.20944/preprints202303.0502.v1
APA Style
Sheikh, B.A., Bhat, B.A., Zareen, H., Rizvi, M.A., Ahmad, Z., Alkhanani, M., Almilaibary, A., Alsagaby, S.A., & Mir, M.A. (2023). Antituberculosis Propensity of Synthetic Biscoumarin Derivatives: An In Silico and In Vitro Approach. Preprints. https://doi.org/10.20944/preprints202303.0502.v1
Chicago/Turabian Style
Sheikh, B.A., Suliman A Alsagaby and Manzoor Ahmad Mir. 2023 "Antituberculosis Propensity of Synthetic Biscoumarin Derivatives: An In Silico and In Vitro Approach" Preprints. https://doi.org/10.20944/preprints202303.0502.v1
Abstract
The concerning rise in emergence and prevalence of resistant strains to drugs of M. tuberculosis has ,the prompted researchers to look for new and effective treatments. With this motive, biscoumarins were identified as the lead molecules on a whole-cell-based screening of several less explored low molecular weight bioactive compounds against M. tuberculosis strains. Among the screened biscoumarins, the highest dock score derivatives were synthesized (a-h) using a programmable microwave synthesizer for better yields and reaction control. The synthesized derivatives were evaluated against H37Rv, H37Ra, M. smegmatis, an MDR surrogate model, and other bacterial strains for the structure-activity response. Assessment of the synthesized library against mycobacterial strains led to the identification of compounds (f and d) as lead anti-tuberculosis agents. Compounds (f and d) exhibited less toxicity against human cell lines. At the same time, it displayed enjoyable activity wherein MIC concentrations were observed to be 16- and 32 µg/mL against the susceptible H37Rv, and H37Ra strains of M. tuberculosis and MIC value of 128 µg/mL for M. smegmatis, respectively. For mechanistic insights and identification of drug binding targets, molecular docking and dynamic simulations were employed for a panel of 16 mycobacterial enzymes essential for mycobacterial growth and survival. These in silico studies revealed the DprE1 enzyme as a druggable target for the anti-tuberculosis activity of the selected biscoumarins derivatives. Further investigation is underway in our laboratory, leading to its development as an anti-tuberculosis drug (animal model studies).
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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