6-(4 '-Aryl-1 ',2 ',3 '-triazolyl)-spirostan-3,5-diols and 6-(4 '-Aryl-1 ',2 ',3 '-triazolyl)-7-hydroxyspirosta-1,4-dien-3-ones: Synthesis and analysis of their cytotoxicity

6-(4 '-Aryl-1 ',2 ',3 '-triazolyl)-spirostan-3,5-diols and 6-(4 '-Aryl-1 ',2 ',3 '-triazolyl)-7-hydroxyspirosta-1,4-dien-3-ones: Synthesis and analysis of their cytotoxicity Full article

Journal

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

Output data

Year: 2019, Volume: 151, Article number : 108460, Pages count : DOI: 10.1016/j.steroids.2019.108460

Tags

Spirostanes; Steroids; Diosgenin; Click chemistry; Cytotoxicity

Authors

Mironov Maxim E. ^1,2 , Oleshko Olga S. ² , Pokrovskii Mikhail A. ² , Rybalova Tatyana V. ^1,2 , Pechurov Vladislav K. ² , Pokrovskii Andrey G. ² , Cheresis Sergey V. ² , Mishinov Sergey V. ³ , Stupak Vyacheslav V. ³ , Shults Elvira E. ^1,2

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Branch, Novosibirsk Inst Organ Chem, Lab Med Chem, Lavrentyev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Pirogova Str 2, Novosibirsk 630090, Russia
3	(Данные Web of science) Ya L Tsivian Novosibirsk Res Inst Traumatol & Ort, Dept Neurosurg 1, Frunze Str 17, Novosibirsk 630091, Russia

In an endeavour to develop potent anti-tumor agents from diosgenin, a series of C-6 derived 1,2,3-triazolyl derivatives were designed and synthesized by employing Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition reaction of novel azides - (22R,25R)-6 beta-azidospirostan-3 beta,5 alpha-diol and 6 beta-azido-7 alpha-hydroxyspirosta-1,4-dien-3-one with aryl(hetaryl)alkynes. All the derivatives were evaluated for cytotoxic activity by MTT assay against eight different human cancer cell lines: T-cellular leucosis (CEM-13), human monocytes (U-937), breast (MDA-MB-231, BT-474), prostate (DU-145) and glioblastoma (U-87MG, SNB-19, T98G). The results of this study suggested that 6-(4'-aryl-1',2',3'-triazolyl)spirostan-3,5-diols 2, 3, 4, 5 and 6 possessed a promising cytotoxic potential. The corresponding 6-substituted 7-hydroxy-1,4-spirostadien-3-ones shown less cytotoxity on the human cancer cells. Compounds 2, 3, 4, and 5 which demonstrated high grown inhibition against glioma cancer cells U-87 and T98G, and also on the human-derived N118669 primary glioblastoma cell line (with GI(50) values in the range of 5-9 mu M), were not affected the growth of SNB-19 cells. The data revealed that phenyl, 4-methoxyphenyl, 4-fluorophenyl, 3,4,5-trimethoxyphenyl or 2-pyridinyl substituent in the triazole moiety at the C-6 position significantly improved the anti-tumor activity. The mentioned position at the spirostan core may be favourable for the synthesis of potent anticancer leads from diosgenin.

Mironov M.E. , Oleshko O.S. , Pokrovskii M.A. , Rybalova T.V. , Pechurov V.K. , Pokrovskii A.G. , Cheresis S.V. , Mishinov S.V. , Stupak V.V. , Shults E.E.
6-(4 '-Aryl-1 ',2 ',3 '-triazolyl)-spirostan-3,5-diols and 6-(4 '-Aryl-1 ',2 ',3 '-triazolyl)-7-hydroxyspirosta-1,4-dien-3-ones: Synthesis and analysis of their cytotoxicity
Steroids. 2019. V.151. 108460 . DOI: 10.1016/j.steroids.2019.108460 WOS Scopus РИНЦ

Published print:

Nov 1, 2019

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