Development of new steroid-based hydrazide and (thio)semicarbazone compounds with anticancer properties.

Autor: Janković ÐD; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia., Šestić TL; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia., Bekić SS; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia., Savić MP; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia. Electronic address: marina.savic@dh.uns.ac.rs., Ćelić AS; Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, Novi Sad 21000, Serbia., Scholda J; Faculty of Life Sciences, Department of Pharmaceutical Sciences, Clinical Pharmacy Group, University of Vienna, Josef-Holaubek-Platz 2, Vienna 1090, Austria., Kopp F; Faculty of Life Sciences, Department of Pharmaceutical Sciences, Clinical Pharmacy Group, University of Vienna, Josef-Holaubek-Platz 2, Vienna 1090, Austria. Electronic address: florian.kopp@univie.ac.at., Marinović MA; Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, Novi Sad 21000, Serbia., Petri ET; Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, Novi Sad 21000, Serbia., Ajduković JJ; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia.
Jazyk: angličtina
Zdroj: The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2024 Sep; Vol. 242, pp. 106545. Date of Electronic Publication: 2024 May 16.
DOI: 10.1016/j.jsbmb.2024.106545
Abstrakt: Most breast and prostate cancers are caused by abnormal production or action of steroidal hormones. Hormonal drugs based on steroid scaffolds represent a significant class of chemotherapeutics that are routinely used in chemotherapy. In this study, the synthesis of new 17a-homo lactone and 17α-(pyridine-2-ylmethyl) androstane derivatives with hydrazide and semicarbazone motifs is presented. All compounds were screened for their effect on cell viability against a panel of five cancer cell lines and one healthy cell line. Two compounds showed significant cytotoxicity against cancer cells, with low toxicity against healthy cells. The relative binding affinities of compounds for the ligand-binding domains of estrogen receptor α, estrogen receptor β, androgen receptor and glucocorticoid receptor were tested using a fluorescence screen in yeast. Potential for inhibition of aldo-keto reductase 1C3 and 1C4 activity was measured in vitro. Experimental results are analyzed in the context of molecular docking simulations. Our results could help guide design of steroid compounds with improved anticancer properties against androgen- and estrogen-dependent cancers.
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 © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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