New class of hybrids based on chalcone and melatonin: a promising therapeutic option for the treatment of colorectal cancer

Considering that conventional chemotherapy provides only a limited increase of overall survival for patients with colorectal cancer (CRC), and resistance is a major cause of therapeutic failure, the emergence of new therapies is needed. Development of different compounds is based on molecular hybridization, which constitutes an effective strategy to inhibit cancer cells and overcome cancer drug resistance. For this purpose, a novel series of chalcone- and melatonin- based hybrids (6a-h) was designed, synthesized, and evaluated for the cytotoxic and antiproliferative effect against SW480 human colon cancer cell line, as well as nonmalignant CHO-K1 cells. All compounds exerted a strong cytotoxic effect against the malignant cell line, with better results than 5-FU, exhibiting half-maximal inhibitory concentration (IC50) values in the range of 0.24 to 4.14 mu M. It is interesting to note that upon 48 h of treatment, hybrid 6f induced a remarkable cytotoxic activity toward SW480 cells (IC50 = 0.26 +/- 0.03 mu M) with lower effect against nonmalignant cells, as evidenced in the selectivity index (SI = 17.38). Additionally, combined calculations on drug-like and pharmacokinetics properties suggested that compound 6f has favorable oral absorption and thus it could be a promising candidate for further studies related to cancer therapy. [GRAPHICS] .