Synthesis, characterization, and anticancer activity of syringaldehyde-derived chalcones against female cancers

A series of novel chalcone analogs derived from syringaldehyde have been synthesized through acid or base-catalyzed aldol condensation. The anticancer activity of the newly synthesized compounds was assessed against a range of women-specific cancer cell lines, including A2780 (ovarian cancer), HeLa and C33a (cervical cancer), and MDA-MB-453, MDA-MB-231 and MCF-7 (breast cancer). The majority of these compounds demonstrated remarkable cytotoxicity against the tested cancer cells. Compound 2a displayed the most promising anti-proliferation activity against the selected female cancer cells, while also exhibiting the weakest cytotoxicity towards human normal cells. Therefore, it was chosen as the active compound based on both drug efficacy and safety considerations in this study. The findings indicated that compound 2a induced cell apoptosis and G2/M phase arrest by causing significant DNA damage and provoking a strong DNA damage response. Moreover, the results indicated that compound 2a affected the phosphorylation and distribution of FAK, thereby inhibiting cell adhesion and migration. Furthermore, compound 2a exhibited excellent potential in inhibiting A2780-derived xenograft tumor growth in mice, without any impact on their body weight. Tissue distribution experiments indicated that compound 2a tended to accumulate in the ovary in vivo. Overall, these results suggest that compound 2a may serve as a promising lead compound for developing anticancer agents against female cancer, especially in the case of ovarian cancer treatment.