Investigation on anticancer agent against cervical and colorectal cancer cell lines: One-pot synthesis, in vitro and in silico assays of xanthone derivatives

Cervical or colorectal cancer disease attracts the world’s attention due to the high mortality in a year. Because of that, an effective anticancer treatment employing an active anticancer agent is urgently needed. Herein, we reported the synthesis and evaluation of the anticancer activity of hydroxylated xanthones against cervical (HeLa) and colorectal (WiDr) cancer cell lines. The hydroxylated xanthones were successfully synthesized through a one-pot reaction between hydroxybenzoic acid and phenolic derivatives in a 6.60-46.50 yield. Their chemical structures have been confirmed using Fourier-transforms infrared, nuclear magnetic resonance, and mass spectrometries. From the in vitro anticancer investigation, 1,3-dihydroxyxanthone exhibited the strongest anticancer activity against HeLa and WiDr cancer cells among the examined hydroxylated xanthones. The 1,3-dihydroxyxanthone gave half-maximal inhibitory concentration and selectivity index values of 0.086-0.114 mM and 2.690-3.591, respectively. The in silico molecular docking studies revealed that 1,3-dihydroxyxanthone interacted with Adenine12, Guanine13, Cytosine14, Arginine503, Glycine504, Lysine505, Isoleucine506, Leucine507, Asparagine520, Alanine521, and Glutamic acid522 through noncovalent forces generating the Gibbs free energy of −6.85 kcal/mol in the active site of Topoisomerase II protein receptor. These results demonstrate that 1,3-dihydroxyxanthone could act as an active anticancer agent against cervical and colorectal cancer cells by inhibiting the Topoisomerase II protein receptor. © 2024, Yehezkiel Steven Kurniawan et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/). All rights reserved.