Cytotoxicity of dihydropyridone and dihydropyrimidone curcumin derivatives against colon (HCT-116) and breast (MDA-MB-231) cancer cell lines

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Breast cancer is the most common invasive cancer and colorectal cancer (CRC) the second most diagnosed malignancy in women worldwide. In men CRC is the third most common cancer. Despite the recent advances in targeted therapy, the clinical efficacy is often limited, noncurative, with a high toxicity profile, and exorbitant costs. Therefore, there is a growing interest in identifying natural compounds that are safe and affordable as adjunctive treatments to the conventional therapy currently offered for these patients. Curcumin from the roots of the Curcuma longa, is one such compound that has become one of the leading and most studied natural medicines for its role in cancer prevention and powerful antioxidant activity. However, its fast metabolism, low bioavailability, and the lack of specificity call for curcumin analogues to be synthesized with increased potency and higher specificity. In search of lead compounds in the present study the cytotoxic effects of curcumin and 14 heterocyclic curcumin derivatives have been screened using the MTT assay on two cancer cell lines HCT-116 and MDA-MB-231 and also on the normal GM08402 (human fibroblast) cell line. Electrochemical oxidation potentials were determined for selected compounds to reveal their electron-donating capacity and as a general indicator of their radical scavenging ability. Two dihydropyridone lead compounds have been identified which compared to curcumin have higher cytotoxicity on both cancer cell lines and at the same time with reduced cytotoxicity on the normal cell line.