Computational exploration and anti-mycobacterial activity of potential inhibitors of Mycobacterium tuberculosis acetyl coenzyme A carboxylase as anti-tubercular agents

ABSTRACT

Acetyl Coenzyme A Carboxylase (AccD6) is a homodimeric protein which is involved in the carboxylation of acetyl coenzyme A to produce malonyl coenzyme A, which plays an important role in the biosynthesis of fatty acid chain. However, studies suggest that AccD6 in combination with AccA3 produces malonyl co-A. Certain herbicides are known to inhibit plant ACC. Among these herbicides, haloxyfop was found to inhibit AccD6 at IC50 of 21.1 ± 1 µM. In this study, we have performed molecular docking of the Maybridge database consisting of ~55,000 compounds in the active site of the protein with haloxyfop as a reference molecule, followed by molecular dynamics study and biological activity determination of prioritized compounds. Out of the nine compounds selected for biological evaluation, three compounds – CD07230, HTS08529 and KM08871 – were found to exhibit anti-mycobacterial activity.

KEYWORDS:

• Docking
• standard precision
• extra precision
• molecular dynamics
• GROMACS

Acknowledgements

CSIR-CDRI chemical repository is acknowledged for providing Maybridge library compounds. JK acknowledges UGC for Senior Research fellowship. This manuscript is a CSIR-CDRI communication number 10189.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplementary data for this article can be accessed at https://doi.org/10.1080/1062936X.2021.1882563