Evaluation of The Anticancer Activity of Hydroxyxanthones Against Human Liver Carcinoma Cell Line

Abstract

Nowadays, cancer is one of the most fatal diseases in developed and developing countries. Therefore, it is an urgent need to find more effective anticancer drugs among the recent commercially available standard drugs. Xanthone derivatives have been researched as anticancer drugs due to their ease of synthesis and structure modification, as well as their excellent anticancer activity. In this work, the in vitro anticancer activity of hydroxyxanthones against the human liver carcinoma cell line (HepG2) was evaluated. Among the twenty-two hydroxyxanthones, 1,3,6,8-tetrahydroxyxanthone was found as the most active anticancer agent with an IC50 value of 9.18 μM, which was better than doxorubicin as the standard drug. From the molecular docking studies against topoisomeraseIIα and two c-KIT protein kinases, 1,3,6,8-tetrahydroxyxanthone yielded strong binding energy in a range of -25.48 to -30.42 kJ/mol. The 1,3,6,8-tetrahydroxyxanthone could bind on the active site of these protein receptors through hydrogen bonds with key amino acid residues (Glu640, Cys673, Gln767, Met769, Asp810, and Asp831), as well as nitrogen bases (Adenine12 and Guanine13), thus leading to the death of HepG2 cancer cells through the apoptosis mechanism.

Molecular Docking and Molecular Dynamic Investigations of Xanthone-Chalcone Derivatives against Epidermal Growth Factor Receptor for Preliminary Discovery of Novel Anticancer Agent

“…It was reported that Gly695, Gly700, Ala719, Glu767, Met769, Arg812, Asp818, Asp831, Gly833, and Tyr845 play a critical role in the catalytic activity of EGFR protein, especially in the suppression of the division of cancer cells [55]. Additionally, Choowongkomon et al [56] reported that there were five active regions in the binding pocket of EGFR receptor, i.e., sugar pocket region, phosphate binding region, adenine region, hydrophobic I and II regions.…”