Synthesis and in vitro assay of hydroxyxanthones as antioxidant and anticancer agents

Abstract

In the present work, three hydroxyxanthones were synthesized in 11.15–33.42% yield from 2,6-dihydroxybenzoic acid as the starting material. The chemical structures of prepared hydroxyxanthones have been elucidated by using spectroscopic techniques. Afterward, the hydroxyxanthones were evaluated as antioxidant agents through radical scavenging assay; and anticancer agents through in vitro assays against WiDr, MCF-7, and HeLa cancer cell lines. Hydroxyxanthone 3b was categorized as a strong antioxidant agent (IC50 = 349 ± 68 µM), while the other compounds were categorized as moderate antioxidant agents (IC50 > 500 µM). On the other hand, hydroxyxanthone 3a exhibited the highest anticancer activity (IC50 = 184 ± 15 µM) and the highest selectivity (SI = 18.42) against MCF-7 cancer cells. From the molecular docking study, it was found that hydroxyxanthone 3a interacted with the active sites of Topoisomerase II protein through Hydrogen bonding with DG13 and π–π stacking interactions with DA12 and DC8. These findings revealed that hydroxyxanthones are potential candidates to be developed as antioxidant and anticancer agents in the future.

Molecular Docking Approach For Design and Synthesis of Thioxanthone Derivatives as Anticancer Agents

“…Fatmasari et al. (2021) reported that the addition of one hydroxyl group on xanthone derivatives decreased their anticancer activity [32] …”

“…Fatmasari et al (2021) reported that the addition of one hydroxyl group on xanthone derivatives decreased their anticancer activity. [32] The anticancer activity of compounds on their inhibition of cell growth was classified into three types: active as anticancer (IC 50 < 20 μg/mL), moderate as anticancer (IC 50 20-100 μg/mL), and inactive as anticancer (IC 50 > 100 μg/mL). [36] Based on the reference, thioxanthone TX3 had moderate activity against T47D (IC 50 86.01 μg/mL), but was inactive against HeLa, A549, and WiDr (IC 50 > 100 μg/mL).…”

“…(2022) also reported the synthesis and anticancer activity of hydroxyxanthone derivatives against WiDr, MCF7, and HeLa cancer cells. The result showed that the addition of one hydroxyl group increase the anticancer activity [32] . On the other hand, Yuanita et al.…”

“…The result showed that the addition of one hydroxyl group increase the anticancer activity. [32] On the other hand, Yuanita et al (2019) reported that the synthesis and anticancer activity of 3,6-dihydroxyxanthone and 4-chloro-3,6-dihydroxyxanthone against T47D and HeLa cancer cells. [33] The result revealed that the addition of one chloro substituent increased the anticancer activity.…”

Synthesis, Cytotoxicity Evaluation and Molecular Docking Studies of Xanthyl-Cinnamate Derivatives as Potential Anticancer Agents

“…It was thoroughly reported that introducing additional substituents to the xanthone skeleton enhances its anticancer activity significantly. For instance, Fatmasari et al [7] reported the synthesis of oxygenated xanthones as the anticancer agent against HeLa, WiDr, and MCF-7; however, these compounds were found to be toxic to normal cells. On the other hand, Yuanita et al [8] have synthesized new xanthone derivatives through the attachment of halogen groups into oxygenated xanthones.…”