Synthesis and Biological Evaluation of New Thiocarbamoylpyrazoline and Chalcone Derivatives on Bone Cancer Cell Lines: In Vitro and In Silico Studies

In the pursuit of multifunctional therapeutic agents, a new series of thiocarbamoylpyrazoline derivatives were synthesized starting from chalcones, and all synthesized compounds (1–12) were structurally characterized using spectroscopic methods (NMR, FT-IR, and Q-TOF-LC-MS) and elemental analysis. The anticancer properties of the test compounds were evaluated in vitro against human bone cancer cell lines MG63 and SW1353 using MTT and LDH assays. LDH assay results demonstrated that the compounds exhibited no detectable cytotoxicity toward normal human chondrocyte (HC) cells. Compared to the reference drug 5-fluorouracil (5-FU), several compounds displayed notable antiproliferative activity. Tumor selectivity index (TSI) analysis identified compounds 1, 2, 4, and 10 as having high tumor selectivity, indicating a preferential cytotoxic effect toward cancer cells over normal cells. Among these, compounds 4 and 10 exhibited the most favorable anticancer profiles, combining potent antiproliferative activity with minimal toxicity to normal cells. Furthermore, to support the experimental anticancer findings, in silico molecular docking studies were performed using the crystal structures of caspase-3 (1GFW), human metalloproteinase-13 (3KEJ), human estrogen receptor (3ERT), and EGFR (1M17) against compounds 1, 2, 4, and 10, and their binding modes were analyzed. © 2026 The Authors. Published by American Chemical Society.