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 Full article

Journal

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

Output data

Year: 2023, Volume: 190, Pages: 109133 Pages count : 1 DOI: 10.1016/j.steroids.2022.109133

Tags

Spirostanes, Steroids, Diosgenin, Click chemistry, Cytotoxicity

Authors

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

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences
2	Novosibirsk State University
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

Submitted:	Sep 1, 2022
Accepted:	Oct 23, 2022
Published online:	Oct 31, 2022

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