Synthesis of fully functionalized spirostanic 1,2,3-triazoles by the three component reaction of diosgenin azides with acetophenones and aryl aldehydes and their biological evaluation as antiproliferative agents

Synthesis of fully functionalized spirostanic 1,2,3-triazoles by the three component reaction of diosgenin azides with acetophenones and aryl aldehydes and their biological evaluation as antiproliferative agents Научная публикация

Журнал

Steroids
ISSN: 0039-128X , E-ISSN: 1878-5867

Вых. Данные

Год: 2023, Том: 190, Страницы: 109133 Страниц : 1 DOI: 10.1016/j.steroids.2022.109133

Ключевые слова

Spirostanes, Steroids, Diosgenin, Click chemistry, Cytotoxicity

Авторы

Mironov Maksim E. ^1,2 , Rybalova Tatyana V. ¹ , Pokrovskii Mikhail A. ² , Emaminia Fatemeh ² , Gandalipov Erik R. ³ , Pokrovskii Andrey G. ² , Shults Elvira E. ¹

Организации

1	Новосибирский институт органической химии им. Н.Н. Ворожцова СО РАН
2	Новосибирский национальный исследовательский государственный университет
3	ITMO University, St. Petersburg, Russia

Diosgenin is of significant interest due to its biological activity and synthetic application. In this study, we report the synthesis of a series of spirostanic 1,4,5-trisubstituted 1,2,3-triazoles by the three component reaction of (25R)-6-azidospirostan-3,5-diols with acetophenones and aryl aldehydes. The one-pot two step synthesis proceeds through the in situ formation of (E)-chalcones and copper catalyzed reaction with organic azides in DMF medium. Structural diversity was achieved by varying the aldehyde and acetophenone nature as well as the spirostanic azide stereochemistry. The results of in vitro biological assays showed that fully decorated spirostanic 1,2,3-triazoles exerted significant and selective antiproliferative activity against MCF-7, glioblastoma (SNB-19, T98G, A-172) and neuroblastoma (IMR-32, SH-SYSY) (HCT116) cell lines (GI50 in the single-digit micromolar range). The data revealed that benzoyl and aryl substitutions in the triazole ring introduced at the 6β-position significantly improved the anti-tumor activity of (25R)-6-azidospirostan-3β,5α-diols. This position on the spirostan core may be the favourable to synthesize of potent anticancer leads from diosgenin.

Mironov M.E. , Rybalova T.V. , Pokrovskii M.A. , Emaminia F. , Gandalipov E.R. , Pokrovskii A.G. , Shults E.E.
Synthesis of fully functionalized spirostanic 1,2,3-triazoles by the three component reaction of diosgenin azides with acetophenones and aryl aldehydes and their biological evaluation as antiproliferative agents
Steroids. 2023. V.190. P.109133. DOI: 10.1016/j.steroids.2022.109133 WOS РИНЦ

Поступила в редакцию:	1 сент. 2022 г.
Принята к публикации:	23 окт. 2022 г.
Опубликована online:	31 окт. 2022 г.

Web of science	WOS:000910436600001
РИНЦ	54068089
OpenAlex	W4307896430