SELECTION OF SECONDARY METABOLITES FROM GARUGA FLORIBUNDA (BURSERACEAE) AS INHA INHIBITORS ON MYCOBACTERIUM TUBERCULOSIS BY IN SILICO

• Main Author: Aulia Alisga, Sitti
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/62765
• Institution: Institut Teknologi Bandung

Tuberculosis (TB) is a deadly disease caused by Mycobacterium tuberculosis (MTB). The cell wall content of Mycobacterium tuberculosis, which is rich in mycolic acid, is the major problem in TB treatment. The impermeability of the cell wall caused by the mycolic acid affects the work of the anti-TB drugs. Isoniazid is the most effective first-line commercial inhibitor against tuberculosis. With the help of KatG, isoniazid becomes active so that it can inhibit InhA, which plays a role in the mycolic acid biosynthesis process. However, isoniazid can cause M. tuberculosis to become resistant to that drug, especially in the KatG gene, causing new problems in TB treatment. Therefore, until now, the search for alternative inhibitors based on natural compounds having antibacterial properties still continues. This research conducted a study on the potential inhibition of nine secondary metabolites of the diphenyl ether and biphenyl diarylheptanoid groups isolated from the bark of Indonesian Garuga floribunda against InhA protein. Initial screening was carried out using the molecular docking method to decide which compounds have anti-tuberculosis potential. Furthermore, to analyze the interaction more accurately, molecular dynamics simulations were carried out. The result of molecular docking simulation showed that the compounds with the best inhibitory potential of the diphenyl ether type and the biphenyl type were garuganin I and Gf-6 compounds. The MMPBSA calculations using molecular dynamics simulations indicated that Whe YalXeV Rf ?Gbind for garuganin I and Gf-6 were í11,5 kcal/mol and í9,3 kcal/mol, respectively. Garuganin I has a better inhibitory potential against InhA than the Gf-6 compound. Garuganin I interacts with InhA through hydrogen bonding with Lys165 and Ile194 residues as well as 14 hydrophobic interactions. Meanwhile, the Gf-6 compound interacts with InhA through hydrogen bonding with Tyr158, Lys165, and Thr196 residues as well as 11 hydrophobic interactions. This research showed that hydrophobic interactions on the substrat binding loop contributed significantly to the inhibition strength of Gf-6 and garuganin I towards InhA.