Design, Synthesis, Structural Characterization, and Anticancer Evaluation of Novel Pyrazole–Thiohydantoin Hybrids

Abstract

Synthesis of Seven Novel Pyrazole-Futilized Thiohydantoins (TH1-TH7) through Hydrate Formation, Vilsmeier-Haack Cyclization, Condensation of Thiosemicarbazones and Intramolecular Cyclization Reaction with Ethyl Chloroacetate has been successfully carried out. The synthesis resulted in compounds with Satisfactory to excellent yields. Structural elucidation of the synthesized compounds has been achieved utilizing Fourier Transform Infrared Spectroscopy, 1H and 13C Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry, which revealed the successful preparation of target thiohydantoins. Evaluation of the cytotoxic activity of the synthesized thiohydantoins has been conducted on the human Mammary carcinoma cell line (MCF-7) utilizing the MTT Assay. It was found that among the compounds tested, TH3 showed the highest cytotoxic activity with an IC₅₀ value of 82.98 µg/mL, followed by TH6 and TH4, thus suggesting the importance of having a para-fluoro substituent on the biological activity of the pyrazole-thiohydantoin scaffold. According to molecular docking studies, Suitable interactions between the synthesized derivatives and the target active site were Acquireed, consistent with the experimental cytotoxic data and providing the likely binding modes. A structure-activity relationship study suggests that electron-withdrawing groups have a significant effect on the biological activity of the synthesized compounds. Despite the low antiproliferative activity of these derivatives, it can be concluded from the results of this study that pyrazole-thiohydantoin hybrid derivatives can serve as Satisfactory leads for the development of new potent anti-cancer drugs.