New Chalcone Ester Derivatives as Potential Cytotoxic Agents

Abstract

Chalcones are a group of molecules with recognized biological potential against many diseases, including cancer. Thus, studies on this structure and derivatives have become an attractive chemical strategy to optimize their observed biological activities. One of the synthetic routes used to obtain chalcone derivatives is esterification using either commercial acid chlorides or carboxylic acids. This work focuses on preparing chalcone derivatives and investigating their biological potential against cancer cells. Compound 3'-hydroxychalcone (1) was synthetized by Claisen-Schmidt condensation followed by esterification of the 3'-OH, resulting in eight compounds named 1a-b and 2a-f. All structures were confirmed by ¹H and ¹³C NMR and FT-IR, and cytotoxicity was evaluated in the HCT 116 (colon adenocarcinoma), MCF-7 (breast adenocarcinoma), and CCD-18Co (nontumoral colon fibroblasts) cell lines. Chalcone derivatives were generally more active toward the colon cancer cell line, and 1a and 2b were selected for IC₅₀ determination, presenting IC₅₀ values of approximately 10 μM in HCT 116 cells and above 20 μM in both MCF7 and CDC-18-Co cells, suggesting moderate selectivity. Additionally, we tested compounds 1a and 2b in combination with doxorubicin, but they did not act synergistically with this anthracycline. In conclusion, considering these compounds obtained by the esterification reaction, 1a and 2d showed better results against cytotoxic cells.