Molecular Docking Study on Phytochemicals of Alpinia galanga and Their Derivatives as Inhibitors of β-Ketoacyl Reductase (MabA) of Mycobacterium Tuberculosis: An In-silico Study

Abstract

Introduction: Tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium Tuberculosis (MTB), continues to be a global health problem. Alpinia galanga (Linn.) of the Zingiberaceae family has antitubercular properties, and their mode of action in in-vitro as well as in-vivo conditions is well established. This knowledge of the active phytochemicals of Alpinia galanga has been utilised to identify new potent drugs for MTB. Aim: To perform molecular docking studies of various phytochemicals of Alpinia galanga and their derivatives with β-ketoacyl reductase (MabA) of MTB. Materials and Methods: The present study is an in-silico study conducted in the Bioinformatics facility of the Central Research Laboratory of Tagore Medical College and Hospital, Chennai, Tamil Nadu, India from November 2022 to April 2023. The receptor protein was downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) database. The phytochemicals in. sdf format were downloaded from the PubChem database. The derivatives were prepared by Chemsketch software. Docking was performed using AutoDock Vina with PyRx as the GUI (Graphical User Interface). Postdocking analysis was performed in LigPlot+. Results: Phytochemicals from Alpinia galanga were obtained from the PubChem database and docked with MabA of MTB. The derivatives were further subjected to docking analyses. From the docking study, two molecules, namely, (1E,6Z)-2,4-diamino6-fluoro-1,7-bis(4-hydroxyphenyl)-1-sulfanylhepta-1,6-diene3,5-dione and (2E,6Z,10E)-2,6,9,9-tetrakis(hydroxymethyl) cycloundeca-2,6,10-trien-1-one-ethane (1/1), were found to have good binding energy values. Conclusion: The present study helped us find drug-like molecules that can inhibit the MabA of MTB. Two compounds derived from the phytochemicals of A. galanga were found to have an effective binding capacity to the drug target in-silico. Hence, the outcome of present study has provided a therapeutic strategy for TB, especially for strains of MTB that are drug-resistant.