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

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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)-6β-azidospirostan-3β,5α-diol and 6β-azido-7α-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 GI50 values in the range of 5–9 μM), 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.

Original languageEnglish
Article number108460
Pages (from-to)108460
Number of pages10
JournalSteroids
Volume151
Early online date22 Jul 2019
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • Click chemistry
  • Cytotoxicity
  • Diosgenin
  • Spirostanes
  • Steroids
  • APOPTOSIS
  • STEROIDS
  • SAPONINS
  • DIOSGENIN
  • BIOLOGICAL EVALUATION
  • CELL-CYCLE ARREST

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