Exploration of new thiazolidinones derived from natural verbenone: Design, synthesis, characterization, and in silico evaluation of alkaline phosphatase and carbonic anhydrase-II inhibition activity

Hybrid compounds featuring isoxazole and thiazolidinone nuclei, alongside verbenone, have become pivotal in pharmacological research due to their versatile properties and straightforward synthesis methods. In this study, the hybrid compounds 3–5 were thoroughly analyzed using high-resolution mass spectrometry (HRMS) and ¹H- and ¹³C NMR spectroscopy, confirming the presence of the isoxazoline and thiazolidinone cores. Additionally, text of in vitro cytotoxicity, computational molecular docking and dynamics studies were performed to study the cytotoxic profile and the modes of possible interactions between the synthesized compounds and the biological targets. The cytotoxicity test indicated that product 5 exhibited the highest activity, with IC₅₀ values ranging from 25.87±3.21 to 28.12±3.54 µM against MDA-MB-231 and A-549 cancer cell lines. From a theoretical point of view, the comparative analysis of compounds 3–5 against the references in the in silico study revealed significant interactions for these compounds with the isoenzymes of alkaline phosphatase and carbonic anhydrase.