A newly synthesized thiosemicarbazide derivative trigger apoptosis rather than necroptosis on HEPG2 cell line
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Date
2024
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Abstract
Thiosemicarbazide 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.
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Antineoplastic Agents , Apoptosis , Caspase 3 , Cell Line, Tumor , Cell Proliferation , Hep G2 Cells , Humans , Liver Neoplasms , Molecular Docking Simulation , Molecular Structure , Necroptosis , Semicarbazides , Silicates , Spectroscopy, Fourier Transform Infrared , Titanium , 4 allyl 1 [[6 (4 methoxyphenyl)imidazo[2,1 b]thiazol 3 yl]acetyl]thiosemicarbazide , amino acid , caspase 3 , caspase 8 , caspase 9 , Ki 67 antigen , protein Bax , protein bcl 2 , thiosemicarbazide derivative , unclassified drug , antineoplastic agent , caspase 3 , semicarbazide derivative , silicate , thiosemicarbazide , titanium , titanium silicide , antiproliferative activity , apoptosis , Article , carbon nuclear magnetic resonance , cell structure , controlled study , cytotoxicity , drug binding , drug design , drug structure , drug synthesis , ECV-304 cell line , elemental analysis , Fourier transform infrared spectroscopy , Hep-G2 cell line , human , human cell , immunocytochemistry , immunoperoxidase staining , immunoreactivity , molecular docking , MTT assay , necroptosis , proton nuclear magnetic resonance , structure analysis , apoptosis , cell proliferation , chemical structure , chemistry , Hep-G2 cell line , liver tumor , metabolism , tumor cell line