Design and In Silico Modeling of Heterocyclic-based Xanthone Derivatives as Potential Anticancer Agents Through Tyrosine Kinase Inhibition

Authors

Yehezkiel Steven Kurniawan, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Ervan Yudha, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Nela Fatmasari, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Radite Yogaswara, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Harno Dwi Pranowo, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Eti Nurwening Sholikhah, Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Jumina Jumina, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaFollow

Abstract

Cancer is one of the deadliest diseases nowadays, and tyrosine kinase receptors play crucial roles in cancer cell survival, differentiation, proliferation, and migration. This study designed and developed a new inhibitor from heterocyclic-based xanthone derivatives to target two tyrosine kinase receptors, epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR), through in silico screening. Eighteen heterocyclic-based xanthones were evaluated through molecular docking for both receptors. All heterocyclic-based xanthones gave the root mean square deviation (RMSD) value lower than 2.00 Å. Xanthone with isobenzothiazole substituent (iBzThio) was found as the most potent inhibitor with binding energies of -10.60 and -12.90 kcal/mol against EGFR and PDGFR, respectively. Further investigation has been performed through molecular dynamics (MD) simulation for 100 ns. From the results of MD simulations, i.e., RMSD, root mean square fluctuation, radius of gyration, solvent accessible surface area, hydrogen bonds, and binding energy parameters, as well as secondary structure fraction, dictionary of protein secondary structure, and Ramachandran plot, iBzThio demonstrated good stability to interact with the active site of both receptors. The binding energies of IBzThio against EGFR and PDGFR receptors were -12.58 and -12.61 kcal/mol after the MD simulations, indicating its potential application as an effective tyrosine kinase inhibitor.

Recommended Citation

Kurniawan, Yehezkiel Steven; Yudha, Ervan; Fatmasari, Nela; Yogaswara, Radite; Pranowo, Harno Dwi; Sholikhah, Eti Nurwening; and Jumina, Jumina (2026) "Design and In Silico Modeling of Heterocyclic-based Xanthone Derivatives as Potential Anticancer Agents Through Tyrosine Kinase Inhibition," Makara Journal of Science: Vol. 30: Iss. 1, Article 5.
DOI: 10.7454/mss.v30i1.2745
Available at: https://scholarhub.ui.ac.id/science/vol30/iss1/5