Synthesis and Study of Substituted Chalcones Combined with Fluoroazobenzenes—New Photoswitches for Application in Biological Systems

Chalcones have garnered significant research interest due to their various medical bioactivities. Several chalcone compounds have been approved for marketing and clinical use in the treatment of various diseases. A critical aspect of the action of chalcones is their effect on microtubules. They are considered an excellent target for chemotherapeutic agents for the treatment of cancer. Consequently, scientists are constantly developing novel chalcone drug agents and also innovative drug delivery strategies. In this manuscript, we report the first synthesis of 12 new visible-light-activated, photoswitchable chalcone-based microtubule inhibitors (17a-17l). Among the obtained compounds, one photoswitch demonstrated light-dependent cytotoxicity in the PC-3 cancer cell line. The IC₅₀ value of the <i>Z</i> conformer was determined to be 4.75 ± 1.00 μM after 48 h of treatment. The <i>E</i> conformer exhibited slightly lower activity compared to the <i>Z</i> conformer, with an IC₅₀ value of 5.80 ± 0.80 µM following 48 h of incubation. In this study, NMR and UV spectroscopy, along with computational methods, were employed.