In Silico Study of Pretomanid: ADME Evaluation and Molecular Docking for Anti-Tubercular Activity
Abstract
One of the deadliest infectious diseases globally is tuberculosis (TB) due to the appearance of drug-resistant strains of the disease, such as multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB). Pretomaind is a new drug that has become increasingly vital in treating resistant TB and it successfully fights against the deadly bacteria known as 'Mycobacterium tuberculosis'. This essay covers its features, mechanism of action, efficiency, safety and overall importance in the fight against TB. Pretomaind works against the tuberculosis bacteria by inhibiting the building up of its cell walls, as well as releasing toxic compounds to kill all bacteria including those not in their active form. Patients on bedaquiline, linezolid and pretomaind (BPaL) treatment were seen to recover quicker and take less time in studies and have certain limitations such as the tendency to cause liver toxicity, stomach irritation, nerve damage and others that need close monitoring. Overall, pretomaind seems to be a vital addition to combat drug-resistant TB, which will in time further reduce tuberculosis around the world.
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References
Stancil SL, Mirzayev F, Abdel-Rahman SM. Profiling Pretomanid as a therapeutic option for TB infection: evidence to date. Drug Des Devel Ther. 2021;15:2815–2830. doi:10.2147/DDDT.S281639.
Baptista R, Fazakerley DM, Beckmann M, Baillie L, Mur LAJ. Untargeted metabolomics reveals a new mode of action of pretomanid (PA-824). Sci Rep. 2018;8(1):5084. doi:10.1038/s41598-018-23110-1.
Patel VP, Tripathi RKP, Dharamsi A. Computational exploration of isatin derivatives for InhA inhibition in tuberculosis: molecular docking, MD simulations and ADMET insights. Curr Comput Aided Drug Des. 2025;21(2):226–254. doi:10.2174/0115734099333313240909103833.
Debnath U, Roy KK, Kumar A. Thiazole-scaffold-based antitubercular agents: a review on synthesis and structural modifications. Synlett. 2025;36(17):2705–2731. doi:10.1055/a-2637-7462.
Kim YM, Park Y, Son ES, et al. Design, synthesis, biological evaluation study of spirocyclic POM analogues as novel MmpL3 anti-tubercular agent. Bioorg Chem. 2024;153:107823. doi:10.1016/j.bioorg.2024.107823.
Yadav R, Meena D, Singh K, Tyagi R, Yadav Y, Sagar R. Recent advances in the synthesis of new benzothiazole based anti-tubercular compounds. RSC Adv. 2023;13(32):21890–21925. doi:10.1039/D3RA03862A.
Nyijime TA, Shallangwa GA, Uzairu A, et al. Computational design and evaluation of hydrantoin derivatives as potential anti-tubercular agents: insight from ADMET, molecular docking, DFT, and molecular dynamic simulations. Lett Drug Des Discov. 2025;22(9):100155. doi:10.1016/j.lddd.2025.100155.
Parveen U, et al. Pretomanid: a novel therapeutic paradigm for treatment of drug-resistant tuberculosis. Indian J Tuberc. 2021.
World Health Organization. Global Tuberculosis Report 2023. Geneva: WHO Publications; 2023.
Pai M, Behr MA, Dowdy D, et al. Tuberculosis. Nat Rev Dis Primers. 2016;2:16076. doi:10.1038/nrdp.2016.76.
Conradie F, Diacon AH, Ngubane N, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893–902.
Keam SJ. Pretomanid: first approval. Drugs. 2019;79(16):1797–1803.
Conradie F, Diacon AH, Ngubane N, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893–902.
World Health Organization. WHO Consolidated Guidelines on Tuberculosis: Module 4 – Treatment of Drug-Resistant Tuberculosis. Geneva: World Health Organization; 2024.
National Center for Biotechnology Information. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury: Pretomanid. Bethesda (MD): NCBI; 2019.
Efficacy and safety of pretomanid-containing regimens in drug-resistant tuberculosis. Eur Respir J. 2025.
World Health Organization. WHO Consolidated Guidelines on Tuberculosis: Drug-Resistant Tuberculosis Treatment. Geneva: World Health Organization; 2024.
Computational drug discovery approaches for anti-tubercular agents. Int J Mol Sci. 2024.
Molecular docking studies of Pretomanid against Mycobacterium tuberculosis.J Biomol Struct Dyn. 2024.
Pretomanid and Ddn enzyme interaction in drug-resistant tuberculosis. Eur Respir J. 2025.
In silico molecular docking and dynamics simulation of anti-tubercular compounds. Sci Rep. 2024.
ADMET prediction and molecular dynamics simulation in tuberculosis drug research. Front Pharmacol. 2025.
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Copyright (c) 2026 Komal P. Miskin, Prabhakar K. Ovhal, Sandhya P. Kadam

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