This paper describes the synthesis of a new A-homo lactam D-homo lactone androstane derivative from dehydroepiandrosterone. To evaluate the impact of the introduction of nitrogen in the parental scaffold on biological activity, a new androstane enamide-type lactam derivative was prepared and characterized. The new compound as well as starting compounds were screened for cytotoxic, anti-angiogenic and anti-inflammatory activities using several human cancer cell lines (MCF-7, MDA-MB-231, PC3, CEM, G-361, HeLa), endothelial (HUVEC) and non-tumour (MRC-5 and BJ) cell lines. Strong cytotoxic and anti-inflammatory activity with a broad therapeutical window was demonstrated by the A-homo lactam D-homo lactone androstane derivative. The induction of apoptosis in treated PC3 cultures was confirmed using apoptotic morphology screening and a fluorescent double-staining method. New A-homo lactam D-homo lactone androstane derivative induced apoptosis more than the tested reference compounds, Formestane and Doxorubicin. An in silico ADME analysis showed that the compounds possess drug-like properties.

Department of Chemistry Biochemistry and Environmental Protection Faculty of Sciences University of Novi Sad Trg Dositeja Obradovića 3 21000 Novi Sad Serbia

Laboratory of Growth Regulators Faculty of Science Palacký University and Institute of Experimental Botany of the Czech Academy of Sciences Šlechtitelů 27 CZ 78371 Olomouc Czech Republic

Oncology Institute of Vojvodina Faculty of Medicine University of Novi Sad Put Dr Goldmana 4 21204 Sremska Kamenica Serbia

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