Synthesis, characterization, anticancer activity of novel chalcone derivatives and the efficacy of electroporation

Abstract

Cancer remains a major life-threatening disease, and the discovery or synthesis of novel cytotoxic agents is a globally pursued research objective. In this study, chalcone-sulfonate compounds containing different heterocycle motifs were synthesized for the first time and evaluated for their anticancer activity. Chalcone-sulfonate derivatives containing new heterocycle motifs were characterized using various spectroscopic techniques such as ¹H NMR, ¹³C NMR and HRMS. The anticancer activities of the newly synthesized chalcone–sulfonate derivatives were evaluated in A549 lung cancer cells, while their biocompatibility was assessed in the L-929 fibroblast cell line using the MTT assay. Additionally, the efficacy of electroporation (EP) on the cytotoxicity of these compounds in the A549 cancer cells was examined. Based on the study's findings all chalcone derivatives exhibited selective anticancer activity, with lower IC₅₀ values on cancer cells compared to fibroblast cells. Compound 4 demonstrated the highest selectivity toward cancer cells (IC₅₀ = 27.40 µM, selectivity index (SI) = 4.54), followed by compound 1 (IC₅₀ = 63.04 µM, SI = 3.26). Compounds 2 (IC₅₀ = 36.38 µM, SI = 2.43) and 3 (IC₅₀ = 56.34 µM, SI = 2.49) showed moderate selectivity. Co-administration of EP with the compounds resulted in substantially greater anticancer activity than treatment with the compounds alone (p < 0.05). In conclusion, chalcone derivatives, particularly compounds 1 and 4, exhibited significant anticancer activity in A549 cells, may represent promising candidates for further investigation as potential chemotherapeutic agents for lung cancer treatment. Their combined use with EP appears to yield promising results, suggesting enhanced therapeutic efficacy.