Abstract
Objective: This study explores vitamin drug conjugates, linking drugs to targeting moieties (Niacin and Pantothenic acid), aiming to enhance TB drug efficacy, reduce dosing frequency, and minimize toxicity. Methods: Isoniazid-Niacin (INH-NIA), Isoniazid-Pantothenic Acid (INH-PA), and Pyrazinamide-Niacin (PYZ-NIA) conjugates were synthesized. Their anti-mycobacterial activity against Mycobacterium smegmatis was evaluated. Molecular docking and molecular dynamics simulations assessed binding affinity and stability with MTb proteases. Drug-likeness and ADME properties were examined. Results: INH-NIA and PYZ-NIA demonstrated significant anti-mycobacterial activity, while INH-PA showed lower activity. Docking and simulations confirmed strong binding with MTb proteases. Drug-likeness and ADME properties supported their potential as antitubercular agents. Discussion: Combining antitubercular drugs with specific vitamins in vitamin drug conjugates offers a promising approach to enhance drug efficacy and reduce resistance. These conjugates provide targeted delivery and improved bioavailability, addressing critical challenges in TB treatment. Molecular dynamics simulations validate the stability of drug-target complexes, reinforcing their potential as antitubercular agents. Conclusions: Vitamin drug conjugates, especially INH-NIA and PYZ-NIA, hold significant promise in combating TB. Their innovative approach may revolutionize TB treatment by addressing drug resistance and improving patient outcomes. Further research is warranted to explore and develop these conjugates as effective tools in the fight against TB. This study underscores the importance of innovative strategies in addressing drug-resistant MTb strains and advancing TB treatment options.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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The authors are thankful to the to the AICTE-RPS project (file no. 8-99/FDC/RPS (POLICY-l)/2019-20) for providing necessary research facilities.
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The authors RPB and PB—designed the experiments; the authors RPB and PB—synthesized the samples and carried out molecular modeling and biological evaluation; the authors RPB and RVC—participated in data processing and contributed to manuscript preparation.
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Bhole, R.P., Bhondave, P.C. & Chikhale, R.V. Assessing the Potential of Vitamin Drug Conjugate for Its Activity against Infectious Disease. Russ J Bioorg Chem 50, 64–75 (2024). https://doi.org/10.1134/S1068162024010151
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DOI: https://doi.org/10.1134/S1068162024010151