IDENTIFYING LEAD COMPOUNDS FOR POTENTIAL ANTI-TUBERCULOSIS DRUGS BY IN SILICO MYCOBACTERIUM TUBERCULOSIS SHIKIMATE KINASE INHIBITORS SELECTION OF CHEMICAL LIBRARY

NUKI BAMBANG NUGROHO; BELLA ETIKA; SRI TEGUH RAHAYU; AJI WIBOWO; EKA SISKA

doi:10.22159/ijap.2025v17i2.52759

Authors

NUKI BAMBANG NUGROHO Research Center for Vaccine and Drug, National Agency for Research and Innovation (BRIN), Cibinong, West Java, Indonesia https://orcid.org/0000-0002-7748-2218
BELLA ETIKA Pharmacy Study Program, Faculty of Health Sciences, Esa Unggul University, Jakarta-11510, Jakarta, Indonesia https://orcid.org/0009-0007-2987-9273
SRI TEGUH RAHAYU Pharmacy Study Program, Faculty of Health Sciences, Esa Unggul University, Jakarta-11510, Jakarta, Indonesia https://orcid.org/0000-0002-2810-160X
AJI WIBOWO Research Center for Vaccine and Drug, National Agency for Research and Innovation (BRIN), Cibinong, West Java, Indonesia https://orcid.org/0009-0000-3804-3151
EKA SISKA Research Center for Vaccine and Drug, National Agency for Research and Innovation (BRIN), Cibinong, West Java, Indonesia

DOI:

https://doi.org/10.22159/ijap.2025v17i2.52759

Keywords:

Mycobacterium tuberculosis, Shikimate pathway, Shikimate kinase, Molecular docking

Abstract

Objective: The present study aimed to identify Shikimate Kinase (SK) inhibitors as antitubercular agents from a chemical library by the utilization of molecular docking simulation, pharmacophore evaluation, and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction approaches.

Methods: A molecular docking study by Molecular Operating Environment (MOE) was used to screen 400,000 compounds from the Mcule ULTIMATE Express 1 chemical library. This docking study used a rigid docking technique to simulate the interaction between receptors and compounds. The screened compounds were then validated by pharmacophore and ADMET analyses to show the presence of positive characteristics.

Results: The result of molecular docking simulation identified N-[2-(diethylamino)ethyl]-2-(pyrrolidin-1-yl)acetamide as the most promising candidate for targeting Mycobacterium tuberculosis Shikimate Kinase (MtSK), due to its binding energy score (-11.3412 kcal/mol) and suitability of interacting residues (Asp34 and Gly80). Moreover, this compound also shared similar pharmacophores with shikimate, and it had positive drug-like and ADMET properties.

Conclusion: This work identified one candidate for SK inhibitor from a pool of five drug-like hit compounds. These inhibitors show promise as prospective candidates for the development of a new anti-tuberculosis therapy and warrant additional experimental investigation.

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