Abstract

This work reports on the development of an efficient and ecofriendly ultrasound assisted method for the high yield synthesis (70.0-94.0%) of eighteen oxyalkylated derivatives of 2',4'-dihydroxychalcone. Synthesized compounds were subjected to in vitro biological assays against HT-29 (colorectal), MCF-7 (breast), and PC-3 (prostate) human tumor cell lines, these cell lines are among the ten most aggressive malignancies diagnosed in the world. Cytotoxicity evaluations showed that four of the synthesized compounds exhibited moderate to very high toxic activity against MCF-7 (IC50 = 8.4-34.3 mu M) and PC-3 (IC50 = 9.3-29.4 mu M) - comparable to 5-fluomuracil (IC50 16.4-22.3 mu M). The same compounds only showed moderate activity against HT-29 (IC50 15.3-36.3 mu M), closer to daunorubicin (IC50 15.1 mu M). Next, although selectivity index (SI) of compounds was weak, compound 18 exhibited a remarkable and selective cytotoxic activity (5.8-10.57) against cancer cells. Outside of these, most compounds significantly reduced cell survival, increased reactive oxygen species (ROS) and caspase activity, and decreased mitochondrial membrane permeability. In this sense, a portion of anti-proliferative activity is due to apoptosis. Notwithstanding, due to its remarkable response, chalcone 18 may be a potential alternative as a chemotherapeutic anti-carcinogen.