Antitumor potential of novel 5α,6β-dibromo steroidal D-homo lactone

[Display omitted] •New steroidal D-homo-3β-hydroxy-5α,6β-dibromo androstane derivative was synthesized.•New steroid compound showed cytotoxic activity against HT-29 and A549 cell lines.•Novel compound has the potential to induce apoptosis in HT-29 cells.•Ligand binding assay suggested a lack of sign...

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Published inSteroids Vol. 188; p. 109118
Main Authors Kuzminac, Ivana Z., Bekić, Sofija S., Ćelić, Anđelka S., Jakimov, Dimitar S., Sakač, Marija N.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.12.2022
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Summary:[Display omitted] •New steroidal D-homo-3β-hydroxy-5α,6β-dibromo androstane derivative was synthesized.•New steroid compound showed cytotoxic activity against HT-29 and A549 cell lines.•Novel compound has the potential to induce apoptosis in HT-29 cells.•Ligand binding assay suggested a lack of significant estrogenic or androgenic properties. New steroidal D-homo androstane derivative, 5α,6β-dibromo-3β-hydroxy-17-oxa-17a-homoandrostan-16-one was synthesized and its structure was confirmed by NMR spectroscopy. In silico ADME properties of this compound were assessed using the SwissADME online prediction tool. Six human cancer cell lines (MDA-MB-231, MCF-7, PC3, HT-29, HeLa, and A549) and one human noncancerous cell line (MRC-5) were used for in vitro cytotoxicity testing. Novel steroidal dibromide was also tested for relative binding affinity for the ligand binding domain of estrogen receptor α and β or the androgen receptor using a published assay in yeast cells. Ligand binding domains of each steroid receptor were expressed in-frame with yellow fluorescent protein in yeast and the fluorescence intensity changes upon addition of test compound was measured. The new compound showed selective cytotoxic activity against HT-29 (colon adenocarcinoma) and A549 (lung adenocarcinoma) cell lines, as well as the potential to induce apoptosis in HT-29 cells, while results obtained from ligand binding assay in yeast suggested a lack of significant estrogenic or androgenic properties.
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ISSN:0039-128X
1878-5867
DOI:10.1016/j.steroids.2022.109118