Title:An In Silico Approach for Identification of Potential Anti-Mycobacterial Targets of Vasicine and Related Chemical Compounds
Volume: 19
Issue: 1
Author(s): Amrita Kashyap Chaliha, Dhrubajyoti Gogoi, Pankaj Chetia, Diganta Sarma and Alak Kumar Buragohain
Affiliation:
Keywords:
Tuberculosis, Justicia adhatoda, vasicine, reverse pharmacophore mapping, molecular docking, Antigen 85C,
bioisosterism.
Abstract: Tuberculosis (TB) is known to mankind as one of the most pervasive and persistent of
diseases since the early days of civilization. The growing resistance of the causative pathogen
Mycobacterium tuberculosis to the standard drug regimen for TB poses further difficulty in its
treatment and control. Screening of novel plant-derived compounds with promising anti-tubercular
activity has been cited as a prospective route for new anti-tubercular drug discovery and design.
Justicia adhatoda L. is a perennial evergreen shrub which is widely mentioned in scientific literature on account of its
potent anti-mycobacterial properties. In the present study, we have employed a series of computational methodologies to
reveal the probable molecular interactions of vasicine, the principal alkaloid of Justicia adhatoda L., and two of its close
natural derivatives- vasicinone and deoxyvasicine, with certain biological targets in M. tuberculosis. Targets were
identified from literature and through a reverse Pharmacophore-based approach. Subsequent comparative molecular
docking to identify the best ligand-target interactions revealed Antigen 85C of M. tuberculosis as the most potent
biological target of vasicine on the basis of optimum molecular docking values. A chemogenomics approach was also
employed to validate the molecular interactions between the same class of chemical compounds as vasicine and Antigen
85C. Further, a library of structural analogs of vasicine was created by bioiosterism-based drug design to identify
structural analogs with better inhibitory potential against Antigen 85C.