Antituberculosis potential of borrelidin derivatives: An in silico molecular docking and molecular dynamic approach

Authors

Teni Ernawati, National Research and Innovation Agency of Republic Indonesia (BRIN)Follow
Donny Ramadhan, National Research and Innovation Agency of Republic Indonesia (BRIN)Follow
Faris Hermawan, National Research and Innovation Agency of Republic Indonesia (BRIN)Follow
Sasmito Wulyoadi, National Research and Innovation Agency of Republic Indonesia (BRIN)Follow
Bambang Marwoto, National Research and Innovation Agency of Republic Indonesia (BRIN)Follow
Ahmad Wibisana, National Research and Innovation Agency of Republic Indonesia (BRIN)Follow
Bambang Srijanto, National Research and Innovation Agency of Republic Indonesia (BRIN)Follow

Abstract

Background: The present tuberculosis (TB) treatment requires a significant time commitment, often lasting from 6 months to 2 years, with strict daily adherence. Non-compliance leads to drug resistance and suboptimal outcomes. Present research indicates that borrelidin shows potential activity against Mycobacterium tuberculosis, including strains that are resistant to first-line medications. Borrelidin has shown remarkable activity against M. tuberculosis H37Rv, with a minimum inhibitory concentration value of 3.12 μg/mL. Therefore, investigating the inhibition activity of borrelidin derivatives was essential for finding new anti-TB candidates. Objectives: This study aims to investigate the effects of 31 borrelidin derivative compounds on M. tuberculosis proteins. Methods: Molecular docking studies were performed on 31 borrelidin compound designs to predict their activity against M. tuberculosis proteins. This was followed by molecular dynamics studies, molecular mechanics-general born-surface area (MM-GBSA), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties predictions. This method can yield the best activity predictions. Results: The docking result revealed that the 31 borrelidin derivatives had binding energies in a range of −8.90 to −10.43 kcaL/moL. These binding energies were higher than rifampin as the native ligand (−13.10 kcaL/moL). However, this is lower than isoniazid (−4.90 kcaL/moL), pyrazinamide (−4.70 kcaL/moL), and moxifloxacin (−7.80 kcaL/moL) as control positives, which is remarkable. During a 100 ns simulation time, borrelidin R₇, R₁₅, R₁₇, and R₂₉ are more stable compared to rifampin as the native ligand. Binding energy calculations using the MM-GBSA method showed that compound R₁₇ has the lowest binding energy. Compound R₁₇ also fulfills ADMET properties, as well as parameters related to ADMET tests. Conclusion: Although borrelidin R₁₇ has limitations due to its unsuitability for transport through the renal organic cation transporter 2 and its inability to act as a substrate for P-glycoprotein (P-gp) or as an inhibitor of P-gp II, based on these findings, borrelidin R₁₇ appears to be the most promising candidate for further evaluation as a new anti-TB agent.

DOI

10.56808/3027-7922.2888

Recommended Citation

Ernawati, Teni; Ramadhan, Donny; Hermawan, Faris; Wulyoadi, Sasmito; Marwoto, Bambang; Wibisana, Ahmad; and Srijanto, Bambang (2025) "Antituberculosis potential of borrelidin derivatives: An in silico molecular docking and molecular dynamic approach," The Thai Journal of Pharmaceutical Sciences: Vol. 49: Iss. 1, Article 7.
DOI: https://doi.org/10.56808/3027-7922.2888
Available at: https://digital.car.chula.ac.th/tjps/vol49/iss1/7