Synthesis and biological evaluation of thiosemicarbazone derivatives

Autor: Meliha Burcu Gürdere, Murat Doğan, Ümit M. Koçyiğit, Mustafa Ceylan, Yakup Budak
Přispěvatelé: Eczacılık Fakültesi
Rok vydání: 2022
Předmět:
Zdroj: Medical Oncology. 39
ISSN: 1559-131X
DOI: 10.1007/s12032-022-01784-y
Popis: In this study, firstly, 22 thiosemicarbazone derivatives (3a-y) were synthesized. Then, ADME parameters, pharmacokinetic properties, drug-like structures, and suitability for medicinal chemistry of these molecules were studied theoretically by using SwissADME and admetSAR programs. According to the results of these theoretical studies, it can be said that the bioavailability and bioactivity of these compounds may be high. In silico molecular docking between ligands (thiosemicarbazone derivatives) and targeted proteins (protein-78 (GRP78) for C6 and quinone reductase-2 (4ZVM for MCF 7) was analyzed using Hex 8.0.0 docking software. According to the docking data, almost all molecules had higher negative E values than Imatinib (already used as drug). For this, in vitro anticancer studies of these molecules were done. The cytotoxic activities of thiosemicarbazone derivatives (3a-y) were evaluated on C6 glioma and MCF7 breast cancer cell lines at 24 hours, and Imatinib was used as positive control. According to the results of cytotoxicity assay, it can be said that the five compounds (3b, c, f, g and m with IC50 = 10.59–9.08; Imatinib IC50 = 11.68) showed more potent cytotoxic activity than Imatinib on C6 cell line. Together with to these results ten compounds (3b, d, f, g, I, k, l, m, n and r with IC50 = 7.02–9.08; Imatinib IC50 = 9.24) had more effective cytotoxic activity against MCF7 cell line than Imatinib. Compound 3m showed the highest antiproliferative effect against C6 and MCF7 cell lines.
Databáze: OpenAIRE
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