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ORIGINAL RESEARCH article

Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1524607
This article is part of the Research Topic Medicinal Chemistry for Neglected Tropical Diseases Using In-vitro, In-vivo and In Silico Approaches View all 5 articles

Microbial-based natural products as potential inhibitors targeting DNA gyrase B of Mycobacterium tuberculosis: An in silico study

Provisionally accepted
Tilal Elsaman Tilal Elsaman 1*Magdi Awadalla Mohamed Magdi Awadalla Mohamed 1*Malik Suliman Mohamed Malik Suliman Mohamed 2Eyman Mohamed Eltayib Eyman Mohamed Eltayib 2Abualgasim Elgaili Abdalla Abualgasim Elgaili Abdalla 3
  • 1 Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, Saudi Arabia
  • 2 Department of Pharmaceutics, College of Pharmacy., Jouf University, Sakakah, Al Jawf, Saudi Arabia
  • 3 College of Applied Medical Sciences, Al Jouf University, Sakaka, Saudi Arabia

The final, formatted version of the article will be published soon.

    Introduction: Since the emergence of Mycobacterium tuberculosis (MBT) strains resistant to most currently used anti-tubercular drugs, there has been an urgent need to develop efficient drugs capable of modulating new therapeutic targets. Mycobacterial DNA gyrase is an enzyme that plays a crucial role in the replication and transcription of DNA in MBT. Consequently, targeting this enzyme is of particular interest in developing new drugs for the treatment of drug-resistant tuberculosis, including multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Methods: In the present study, multiple computational tools were adopted to screen a microbial-based natural products database (NPAtlas) for potential inhibitors of the ATPase activity of MBT DNA gyrase. Results and Discussion: Twelve hits were initially identified as the top candidates based on their docking scores (ranging from ‒9.491 to ‒10.77 kcal/mol) and binding free energies (‒60.37 to ‒73.21 kcal/mol). Following this, computational filters, including ADME-T profiling and pharmacophore modeling, were applied to further refine the selection. As a result, three compounds 1-Hydroxy-D-788-7, Erythrin, and Pyrindolol K2 emerged as the most promising, exhibiting favorable drug-like properties. Notably, 1-Hydroxy-D-788-7, an anthracycline derivative, demonstrated superior binding affinity in molecular dynamics simulations. The RMSD values, ranging from 1.7 to 2.5 Å, alongside RMSF analysis and a detailed evaluation of the established interaction forces, revealed that 1-Hydroxy-D-788-7 was the strongest binder to Mycobacterial DNA Gyrase B. The stable binding and favorable interaction profile highlighted 1-Hydroxy-D-788-7 as a top hit. These comprehensive computational findings strongly support the potential of 1-Hydroxy-D-788-7 as an effective anti-TB lead compound, warranting further experimental validation to confirm its therapeutic efficacy.

    Keywords: Mycobacterium tuberculosis, DNA gyrase B, Natural Products, Virtual Screening, Resistance

    Received: 07 Nov 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 Elsaman, Mohamed, Mohamed, Eltayib and Abdalla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Tilal Elsaman, Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, Saudi Arabia
    Magdi Awadalla Mohamed, Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, Saudi Arabia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.