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. 2025 Jan;17(1):19-34.
doi: 10.1080/17568919.2024.2444872. Epub 2024 Dec 25.

Developing novel indoles as antitubercular agents and simulated annealing-based analysis of their binding with MmpL3

Rajdeep Ray  1 , Stutee Das  1 , Sumit Raosaheb Birangal  1 , Helena I Boshoff  2 , Jose Santinni Roma  2 , Manisha Lobo  1 , Raghu Chandrashekhar Hariharapura  3 , G Gautham Shenoy  1
Affiliations

Developing novel indoles as antitubercular agents and simulated annealing-based analysis of their binding with MmpL3

Rajdeep Ray et al. Future Med Chem. 2025 Jan.

Erratum in

  • Correction.
    [No authors listed] [No authors listed] Future Med Chem. 2025 Aug 26:1. doi: 10.1080/17568919.2025.2552567. Online ahead of print. Future Med Chem. 2025. PMID: 40856627 No abstract available.

Abstract

Aim: This research aimed to develop novel indole-2-carboxamides as potential antitubercular agents using rational drug design. It also focused on identifying the critical interactions required for these compounds to exhibit effective antitubercular activity.

Materials and methods: Novel indole-2-carboxamides targeting MmpL3 were designed based on SAR, synthesized, and tested for their antitubercular and iniBAC induction properties. Classical docking and simulated annealing were utilized to understand protein-ligand binding affinity.

Results: Compounds 5c, 5f, and 5i, were active against H37Rv and different MDR and XDR strains of M. tuberculosis. iniBAC promoter induction study indicated that those were inhibitors of MmpL3. Through the docking and simulated annealing studies, we identified key protein-ligand interactions at the MmpL3 binding site.

Conclusion: We have identified three potent antitubercular molecules that supposedly act via inhibiting MmpL3. Results from the molecular modeling studies can be used in future drug designing.

Keywords: MmpL3; indole-2-carboxamides; molecular docking; simulated annealing; tuberculosis.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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References

    1. World Health Organisation . Global tuberculosis report. 2023. Available from: https://www.who.int/teams/global-tuberculosis-programme/tb-reports/globa...
    1. WHO consolidated guidelines on tuberculosis, module 4: treatment - drug-susceptible tuberculosis treatment. n.d.. Available from: https://www.who.int/publications/i/item/9789240048126 - PubMed
    1. Tballiance.org . FDA approves new treatment for highly drug-resistant forms of tuberculosis | TB alliance. [Online]. 2019. Available from: https://www.tballiance.org/news/fda-approves-new-treatment-highly-drug-r...
    1. Mahajan R. Bedaquiline: first fda-approved tuberculosis drug in 40 years. Int J Appl Basic Med Res. 2013;3(1):1–2. doi: 10.4103/2229-516X.112228 - DOI - PMC - PubMed
    1. Melly G, Purdy GE.. MmpL proteins in physiology and pathogenesis of M. tuberculosis. Microorganisms. 2019;7(3):70. doi: 10.3390/microorganisms7030070 - DOI - PMC - PubMed

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