Mono- and bis(steroids) containing a cyclooctane core: Synthesis, antiproliferative activity, and action on cell cytoskeleton microtubules.
antiproliferative activity
estradiol
steroid dimers
triazoles
tubulin
Journal
Archiv der Pharmazie
ISSN: 1521-4184
Titre abrégé: Arch Pharm (Weinheim)
Pays: Germany
ID NLM: 0330167
Informations de publication
Date de publication:
30 Jul 2024
30 Jul 2024
Historique:
revised:
12
07
2024
received:
13
06
2024
accepted:
15
07
2024
medline:
31
7
2024
pubmed:
31
7
2024
entrez:
30
7
2024
Statut:
aheadofprint
Résumé
Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring-opening of mono- and polyoxiranes, containing a cyclooctane core, by azide-anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper-catalyzed azyde-alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.
Identifiants
pubmed: 39079938
doi: 10.1002/ardp.202400483
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2400483Subventions
Organisme : State research program "Molecular design, synthesis and study of physiologically active compounds, advancing the methodology of medicinal chemistry, chemoinformatics, and targeted chemical synthesis"
ID : 121021000105-7
Informations de copyright
© 2024 Deutsche Pharmazeutische Gesellschaft.
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