New A-homo lactam D-homo lactone androstane derivative: Synthesis and evaluation of cytotoxic and anti-inflammatory activities in vitro

0531060 - ÚEB 2021 RIV US eng J - Journal Article
Savić, M. P. - Škorić, D. - Kuzminac, I. Z. - Jakimov, D. S. - Kojić, V. V. - Rárová, Lucie - Strnad, Miroslav - Djurendić, E. A.
New A-homo lactam D-homo lactone androstane derivative: Synthesis and evaluation of cytotoxic and anti-inflammatory activities in vitro.
Steroids. Roč. 157, MAY (2020), č. článku 108596. ISSN 0039-128X. E-ISSN 1878-5867
R&D Projects: GA ČR(CZ) GA19-01383S
Institutional support: RVO:61389030
Keywords : ADME analysis in silico * Anti-angiogenic activity * Anti-inflammatory activity * Apoptotic morphology * Cytotoxic activity * Structural analysis
OECD category: Organic chemistry
Impact factor: 2.668, year: 2020
Method of publishing: Open access
http://doi.org/10.1016/j.steroids.2020.108596

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.
Permanent Link: http://hdl.handle.net/11104/0309810