The Journal of Pure and Applied Chemistry Research
Vol. 14 No. 1 (2025): Edition January-April 2025

Design, Synthesis, and In Silico Study of Two N-Substituted Pyrazinamide Analogs as Potential Antituberculosis Agents

Zulqurnain, Muhammad (Unknown)
Wati, First Ambar (Unknown)
Nurjanah, Ana (Unknown)
Kavin, Layli Adha Nadira (Unknown)
Afifah, Rizqi Nur (Unknown)
Suyatno (Unknown)
Santoso, Mardi (Unknown)



Article Info

Publish Date
08 Apr 2025

Abstract

Tuberculosis (TB) is an infectious yet often overlooked disease that remains a significant global challenge. Pyrazinamide (PZA), a key drug in the first-line TB treatment regimen, is used to reduce the duration of therapy, making it a compound of great interest for further exploration. Two pyrazine-2-carboxamide analogs have been successfully synthesized and reported, followed by an in-silico evaluation of their potency as antituberculosis agents. Yamaguchi reagent was employed as a coupling agent between pyrazine-2-carboxylic acid and corresponding amine, yielding N-(cyclohexylmethyl) pyrazine-2-carboxamide (D) and N-(4-cyclooctyl) pyrazine-2-carboxamide (E) in 60% and 55%, respectively. The molecular docking analysis of compounds (D) and (E) demonstrated lower binding energies (-7.65 and -7.37 kcal/mol, respectively), in comparison with the standard TB drugs, pyrazinamide and isoniazid. Additionally, ADME and pharmacokinetics evaluations revealed that compounds (D) and (E) meet the essential criteria for oral drug candidacy. These findings suggest that the pyrazinamide analogs (D) and (E) hold significant potential as promising antimycobacterial agents for tuberculosis therapy.

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Journal Info

Abbrev

jpacr

Publisher

Subject

Chemical Engineering, Chemistry & Bioengineering Chemistry Materials Science & Nanotechnology Medicine & Pharmacology

Description

The Journal of Pure and Applied Chemistry Research focuses in publishing research articles in the field of Chemistry and Applied Chemistry. The target is in exploring, investigating, and developing chemicals sources from local and/or Indonesian to increase the value. Scope of the journal is organic ...