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

Florian Kopp, Tijana Lj Šestić, Jovana J Ajduković, Sofija S Bekić, Andjelka S Ćelić, Maja A Marinović, Edward T Petri, Marina P Savić, Ðorđe D Janković, Julia Scholda

Journal: The Journal of steroid biochemistry and molecular biology 2024;242():106545

PMID: 38762058

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia.; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia. Electronic address: [email protected].; Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, Novi Sad 21000, Serbia.; Faculty of Life Sciences, Department of Pharmaceutical Sciences, Clinical Pharmacy Group, University of Vienna, Josef-Holaubek-Platz 2, Vienna 1090, Austria.; Faculty of Life Sciences, Department of Pharmaceutical Sciences, Clinical Pharmacy Group, University of Vienna, Josef-Holaubek-Platz 2, Vienna 1090, Austria. Electronic address: [email protected].

DOI: 10.1016/j.jsbmb.2024.106545

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MeSH Terms: Humans, Antineoplastic Agents, Molecular Docking Simulation, Hydrazines, Cell Line, Tumor, Cell Survival, Steroids, Semicarbazones, Thiosemicarbazones, Drug Screening Assays, Antitumor