Anticancer activity and ADME–toxicity evaluation of novel synthesized chalcone-sulfonate derivatives in osteosarcoma cells and the effect of electroporation

This study aimed to synthesize and characterize novel chalcone-sulfonate derivatives and evaluate their cytotoxicity, selectivity, and electroporation (EP)-enhanced activity against U2OS osteosarcoma cells. Twelve chalcone-sulfonate derivatives were synthesized and characterized by 1H NMR, 13C NMR, and HRMS analyses. The electron-withdrawing substituents (4-Cl, 4-Br, NO2, dichloro, trichloro), electron-releasing substituents (methyl, trimethyl, tertiary‑butyl), heterocyclic motifs (thiophene, pyridyl, quinoline), and bulky groups (biphenyl, naphthyl) were used on novel chalcone-sulfonate derivatives. The cytotoxicity of the newly synthesized compounds was assessed in U2OS osteosarcoma cells and normal BEAS-2B cells using the MTT assay. The effects of EP on the activity of selected derivatives were also investigated. Derivatives 7 and 8 exhibited the highest cytotoxic activity among the tested compounds, with IC50 values of 87.50 and 74.09 μM, respectively. Although doxorubicin showed greater cytotoxicity, derivatives 7 and 8 exhibited higher selectivity indices (2.0 and 3.7, respectively) than doxorubicin (1.1). EP enhanced the activity of derivatives 7 and 8 by 2.56- and 2.42-fold, respectively. Derivatives 7 and 8 warrant further investigation and structural optimization for their activity against U2OS osteosarcoma cells, particularly in combination with EP.