Synthesis and biological evaluation of xanthone derivatives as anti-cancer agents targeting topoisomerase II and DNA

• Published in: Medicinal chemistry research Vol. 31; no. 5; pp. 720 - 734
• Main Authors: Song, Yali, Zhu, Xinyue, Yang, Kan, Feng, Siran, Zhang, Yiwen, Dong, Jinjiao, Liu, Zhenming, Qiao, Xiaoqiang
• Format: Journal Article
• Language: English
• Published: New York Springer US 2022; Springer Nature B.V
• Subjects: Anticancer properties; Antitumor agents; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Breast cancer; Cancer; Cervical cancer; Cervix; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA topoisomerase; DNA topoisomerase (ATP-hydrolysing); Enzymatic activity; Enzyme activity; Gastric cancer; Hydrogen bonding; Hydrogen bonds; Inorganic Chemistry; Medicinal Chemistry; Molecular docking; Original Research; Pharmacology/Toxicology; Toxicity; Tumor cell lines; Selectivity; Topoisomerase II; Molecular docking; Xanthone derivatives
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-022-02862-6

Topoisomerase is one of the most important targets of anti-cancer drugs. In order to develop effective and low-toxic topoisomerase inhibitors, a series of xanthone derivatives have been designed and synthesized using the principles of skeleton transition. In vitro cytotoxicity assays of human breast cancer (MCF-7), gastric cancer (MGC-803), and cervical cancer(Hela) cell lines, most of the compounds showed antitumor growth activity, and also showed low toxicity to human normal cells L929. In the enzyme activity inhibition experiment, compounds 7d and 8d showed the best inhibitory activity. The DNA binding studies disclosed that the most potent compounds 7d and 8d can intercalate into DNA, induce apoptosis in MGC-803 cells and arrest cells in G2/M phase. Molecular docking showed that compounds 7d and 8d could bind with topoisomerase II and DNA through hydrogen bonds and π-stacking interactions. Graphical abstract