Synthesis of glycol-and amine-containing anthraquinones exhibiting of cytotoxicity, DNA-Binding affinity and apoptosis

Abstract

Cancer is one of the leading causes of death worldwide. This research focuses on the synthesis of a new series of anthracene-9, 10-dione derivatives (2-15) for cancer chemoprotechtive therapy, classified into two series (i) increasing cytotoxic activity in human papillomavirus (HPV) positive cancer cell line. Ca Ski. The highest cytotoxicity was achieved by 4-(benzylamino)-9,10-dioxo-4a,9,9a,10-tettahydroanthracen-1-yl 4-ethylbenzenesulfonate (5) with the inhibitory concentration 50 (IC₅₀) of 0.3 µM which is 20 times lower than that of cisplatin (CDDP; IC₅₀ = 8.0 µM. The toxicity against non-cancerous cell lines, WI-38, was low with the IC₅₀ > 30 µM. The anticancer mechanism of such compound caused decreasing HPV E6 expression. Furthermore, increasing p53 and decreasing Bcl-2 expression was noted. Cell cycle profiles revealed an accumulation of cells in the G₂/M phase and (ii) overcoming drug resistance with remarkable cytotoxic activity, (4-(4-Aminobenzylamino)-9,10-dioxo-9,10-dihydroanthracen -1-yl-4-methylbenzenesulfonate) (9) has excellent cytotoxicity against doxorubicin-resistant cancer cell lines IC₅₀ = 0.8 µM, 20-fold higher than doxorubicin.