Molecular docking and pharmacokinetic prediction of isoniazid and curcumin compounds against N-acetyltransferase 2 (NAT2) protein
Abstract
NAT2 serves as the key enzyme responsible for metabolizing the INH compound, with its expression and functional activity significantly contributing to the risk of hepatotoxicity. Due to the possible inhibitory role of curcumin on NAT2, it is important to assess its effect on the metabolic processing of INH and to examine the enzyme-related interactions that may occur between drugs. Molecular docking studies demonstrated that curcumin can localize in the hydrophobic pocket and form a strong bond with NAT2. The aim of this study was to predict the potential interaction of the isoniazid and curcumin compounds against NAT2 protein. In this study, NAT2 protein (PDB ID: 2PFR) was used as a receptor. The results obtained showed the binding energies of native ligand, isoniazid, and curcumin were -5.78, -4.47, -8.35 kcal/mol, respectively. The findings of this research suggest that curcumin is capable of suppressing NAT2 activity, thereby affecting the pharmacokinetics of INH. These results may offer insights into minimizing INH-related liver toxicity and enhancing its effectiveness through co-administration with curcumin.
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[26] H. Hasrianti and Arwansyah, “Simulasi molecular docking senyawa kurkumin dan analognya sebagai selective androgen receptor modulators (SARMS) pada kanker prostat,” Jurnal Dinamika, vol. 5, no. 2, pp. 60–75, 2014.
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Pharmacology, no. 201, pp. 285–297, 2011, doi: 10.1007/978-3-642-14541-4_7.
[34] Y. A. Cho, W. Lee, and J. S. Choi, “Effects of curcumin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen, in rats: Possible role of CYP3A4 and P-glycoprotein inhibition by curcumin,” Pharmazie, vol. 67, no. 2, pp. 124–130, 2012.
[35] “Isoniazid,” Tuberculosis (Edinb), vol. 88, no. 2, pp. 112–116, 2008, doi: 10.1016/S1472-9792(08)70011-8.
[36] K. M. Nelson, J. L. Dahlin, J. Bisson, J. Graham, G. F. Pauli, and M. A. Walters, “The essential medicinal chemistry of curcumin,” Journal of Medicinal Chemistry, vol. 60, no. 5, pp. 1620–1637, 2017, doi: 10.1021/acs.jmedchem.6b00975.
[37] A. B. Rowaiye, Y. J. T. Mendes, S. A. Olofinsae, J. B. Oche, O. H. Oladipo, O. A. Okpalefe, and J. O. Ogidigo, “Camptothecin shows better promise than curcumin in the inhibition of the human telomerase: A computational study,” Heliyon, vol. 7, no. 8, 2021, doi: 10.1016/j.heliyon.2021.e07742.
[38] S. P. Rendic, “Metabolism and interactions of ivermectin with human cytochrome P450 enzymes and drug transporters: Possible adverse and toxic effects,” Archives of Toxicology, vol. 95, no. 5, pp. 1535–1546, 2021, doi: 10.1007/s00204-021-03025-z.
[39] W. H. Gaither and V. Gupta, “Drug clearance,” StatPearls, 2023, PMID: 32491690.
[40] S. G. Shin, J. K. Roh, N. S. Lee, J. G. Shin, I. J. Jang, C. W. Park, and H. J. Myung, “Kinetics of isoniazid transfer into cerebrospinal fluid in patients with tuberculous meningitis,” Journal of Korean Medical Science, vol. 5, no. 1, pp. 39–45, 1990, doi: 10.3346/jkms.1990.5.1.39.
[41] H. Xiaoying, L. Guoweli, C. Yuanyuan, and X. Qirning, “Pharmacokinetics and pharmacodynamics of the combination of rhein and curcumin in the treatment of chronic kidney disease in rats,” Frontiers in Pharmacology, vol. 11, no. 1, pp. 1–10, 2020.
Published
2025-11-18
How to Cite
SIMANULLANG, Gayatri et al.
Molecular docking and pharmacokinetic prediction of isoniazid and curcumin compounds against N-acetyltransferase 2 (NAT2) protein.
JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 23, n. 2, p. 305-313, nov. 2025.
ISSN 2614-6495.
Available at: <http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/1699>. Date accessed: 08 dec. 2025.
doi: https://doi.org/10.35814/jifi.v23i2.1699.
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