SCREENING OF ASHITABA (ANGELICA KEISKEI K.) COMPOUNDS AS POTENTIAL MYCOBACTERIUM TUBERCULOSIS KASA INHIBITORS

Abstract

Objective: Tuberculosis (TB) is a major global issue, mainly owing to the emergence of antibiotic-resistant strains of the disease's causative agent, Mycobacterium tuberculosis. The current standard of treatment for tuberculosis entails a prolonged course of antibiotics with toxic side effects and is accompanied by low patient compliance. Therefore, developing and discovering TB medications is critical to obtaining TB drugs that are more effective and sensitive to Mycobacterium tuberculosis. Ashitaba (Angelica keiskei K.) has reported that Ashitaba extract and chalcone have anti-TB properties, but the responsible compound has not been reported yet. This study aimed to identify the profile metabolites present in Ashitaba and their interaction with Mycobacterium tuberculosis KasA. Methods: To suggest these, we used molecular docking and molecular dynamic to predict the interactions of 40 selected compounds from the Ashitaba against Mycobacterium tuberculosis KasA (PDB ID 2WGE). Results: The results of molecular docking identified the top two compounds as xanthoangelol I (XAI) and (2E)-1-[4-hydroxy-2-(2-hydroxy-2-propanyl)-2,3-dihydro-1-benzofuran-7-yl]-3-(4-hydroxyphenyl)-2-propen-1-one (4HH), with bond free energies of-12.03 and-11.87 kcal/mol, respectively. Based on the results of molecular dynamics simulations, the XAI was stronger than 4HH in stabilizing complexes with 2WGE with total energy (ΔGbind, MMGBSA) of-54.8512 and-37.8836 kcal/mol, respectively. Conclusion: It can be concluded that xanthoangelol I (XAI) have the most potent inhibitor of Mycobacterium tuberculosis KasA.