Computational Test of Isoniazid Derivatives as Anti-Mycobacterium tuberculosis Sensitive and Resistant Types
DOI:
https://doi.org/10.56904/jgpr.v1i01.120Keywords:
ADMET, anti-TB, derivative isoniazid, molecular dockingAbstract
The development of antimicrobial drugs through structure modification of existing compounds are aimed at improving therapeutic effects while reducing side effects, toxicity and resistance potential. Isoniazid (INH) is still the first-line choice for TB treatment and isoniazid resistance has been reported in several regions in the world include Indonesia, so develop isoniazid derivatives are needed. This study aimed to predict the anti-tuberculosis potential of isoniazid derivatives using molecular docking method. The research materials were digital data of isoniazid derivatives in SMILES and 3D formats of 18 isoniazid derivatives and Catalase-Peroxidase (KatG) receptor targets of Mycobacterium tuberculosis sensitive and KatG resistant downloaded through www.rscb.org. The implementation of this research includes collecting ligand data from the literature, converting to SMILE and 3D formats using ChemOffice 10, affinity observation using Arguslab 4.01 and Biovia Discovery 2016, and evaluating the pharmacokinetic and toxicity profiles of selected ligands. The results of this study showed that 13 of the 18 INH derivatives had stronger affinity and the same interaction pattern with isoniazid through the formation of hydrogen bonds with Asp 137 against sensitive KatG receptors, and 7 of them did not show the same interaction pattern with isoniazid against resistant KatG receptors through the formation of hydrogen bonds with Arg 104. While evaluating the pharmacokinetic and toxicity profiles of 7 selected INH derivatives, only 3 showed better potential than INH. Thus, several INH derivative candidates are predicted to have better potential anti-tuberculosis effects through an in-silico approach.
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