Novel phenoxyacetylthiosemicarbazide derivatives as novel ligands in cancer diseases.

Autor: Kozyra P; Independent Radiopharmacy Unit, Medical University of Lublin, Chodzki 4a, PL-20093 Lublin, Poland. Electronic address: pawelkozyra@umlub.pl., Adamczuk G; Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland., Karczmarzyk Z; Faculty of Science, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, PL-08110 Siedlce, Poland., Matysiak J; Department of Chemistry, University of Life Sciences in Lublin, Akademicka 15, PL-20950 Lublin, Poland., Podkościelna B; Department of Polymer Chemistry, Faculty of Chemistry, Maria Curie-Sklodowska University in Lublin, Gliniana 33, PL 20-400 Lublin, Poland., Humeniuk E; Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland., Wysocki W; Faculty of Science, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, PL-08110 Siedlce, Poland., Korga-Plewko A; Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland., Senczyna B; Department of Chemistry, University of Life Sciences in Lublin, Akademicka 15, PL-20950 Lublin, Poland., Pitucha M; Independent Radiopharmacy Unit, Medical University of Lublin, Chodzki 4a, PL-20093 Lublin, Poland.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2023 Sep 15; Vol. 475, pp. 116634. Date of Electronic Publication: 2023 Jul 22.
DOI: 10.1016/j.taap.2023.116634
Abstrakt: Numerous epidemiological studies report an increased risk of developing prostate cancer in patients with melanoma and an increased risk of developing melanoma in patients with prostate cancer. Based on our previous studies demonstrating the high anticancer activity of thiosemicarbazides with a phenoxy moiety, we designed nineteen phenoxyacetylthiosemicarbazide derivatives and four of them acting as potential dual-ligands for both cancers. All of the compounds were characterized by their melting points and 1 H, 13 C NMR and IR spectra. For selected compounds, X-ray investigations were carried out to confirm the synthesis pathway, identify the tautomeric form and intra- and intermolecular interaction in the crystalline state. The conformational preferences and electronic structure of molecules were investigated by theoretical calculation method. Lipophilicity of compounds (log k w ) was determined using isocratic reversed phase/high pressure liquid chromatography RP-18. For the obtained compounds, in vitro tests were carried out on four melanoma cell lines (A375, G-361, SK-MEL2, SK-MEL28), four prostate cancer cell lines (PC-3, DU-145, LNCaP, VcaP) and a normal human fibroblast cell line (BJ). The most active compounds turned out to be F6. Cell cycle analysis, apoptosis detection, CellROX staining and mitochondrial membrane potential analysis were performed for the most sensitive cancer cells treated with most active compounds. DSC analysis was additionally performed for selected compounds to determine their purity, compatibility, and thermal stability. The process of prooxidation was proposed as a potential mechanism of anticancer activity.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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