Başoğlu-Ünal F.Becer E.Ensarioğlu H.K.-Güzeldemirci N.U.Kuran E.D.Vatansever H.S.2024-07-222024-07-22202417470277http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/11721Thiosemicarbazide derivatives have been the focus of scientists owing to their broad biological activities such as anticancer, antimicrobial, and anti-inflammatory. Herein, we designed and synthesized a new thiosemicarbazide derivative (TS-1) and evaluated its antiproliferative potential against the human hepatocellular carcinoma cell line (HEPG2) and human umbilical vein endothelial cell line (ECV-304). Also, it was aimed to investigate the necroptotic and apoptotic cell death effects of TS-1 in HEPG2 cells, and these effects were supported by molecular docking. The new synthesized compound structure was characterized using various spectroscopic methods such as FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. The cytotoxic activity of the tested compound was measured by the MTT assay. Apoptotic and necroptotic properties of the TS-1 were evaluated by indirect immunoperoxidase method using antibodies against Ki-67, Bax, Bcl-2, caspase-3, caspase-8, caspase-9, RIP3, and RIPK1. Apoptotic and necroptotic effects of TS-1 were supported by molecular docking. Compound TS-1 was synthesized as a pure compound with a high yield. The effective value of TS-1 was 10 μM in HEPG2 cells. TS-1 did not show any cytotoxic effect on ECV-304. Caspase-3 and RIPK1 immunoreactivities were significantly increased in HEPG2 cells after being treated with TS-1. As the results of the molecular docking studies, the molecular docking showed that the TS-1 exhibits H-bond interaction with various significant amino acid residues in the active site of both RIPK1. It could be concluded that TS-1 could be a promising novel therapeutic agent by inducing apoptosis rather than necroptosis in HEPG2 cells. © 2023 John Wiley & Sons Ltd.EnglishAll Open Access; Bronze Open AccessAntineoplastic AgentsApoptosisCaspase 3Cell Line, TumorCell ProliferationHep G2 CellsHumansLiver NeoplasmsMolecular Docking SimulationMolecular StructureNecroptosisSemicarbazidesSilicatesSpectroscopy, Fourier Transform InfraredTitanium4 allyl 1 [[6 (4 methoxyphenyl)imidazo[2,1 b]thiazol 3 yl]acetyl]thiosemicarbazideamino acidcaspase 3caspase 8caspase 9Ki 67 antigenprotein Baxprotein bcl 2thiosemicarbazide derivativeunclassified drugantineoplastic agentcaspase 3semicarbazide derivativesilicatethiosemicarbazidetitaniumtitanium silicideantiproliferative activityapoptosisArticlecarbon nuclear magnetic resonancecell structurecontrolled studycytotoxicitydrug bindingdrug designdrug structuredrug synthesisECV-304 cell lineelemental analysisFourier transform infrared spectroscopyHep-G2 cell linehumanhuman cellimmunocytochemistryimmunoperoxidase stainingimmunoreactivitymolecular dockingMTT assaynecroptosisproton nuclear magnetic resonancestructure analysisapoptosiscell proliferationchemical structurechemistryHep-G2 cell lineliver tumormetabolismtumor cell lineArticle10.1111/cbdd.14355