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
| Autor: | Sergey V. Cheresis, Olga S. Oleshko, Vladislav K. Pechurov, Tatyana V. Rybalova, M. A. Pokrovskii, Elvira E. Shults, M. E. Mironov, V. V. Stupak, A. G. Pokrovskii, S. V. Mishinov |
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| Rok vydání: | 2019 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Substituent Triazole Antineoplastic Agents 030209 endocrinology & metabolism Chemistry Techniques Synthetic Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Cell Line Tumor Humans Spiro Compounds MTT assay Cytotoxicity Molecular Biology Pharmacology Aryl Organic Chemistry Diosgenin Triazoles Cycloaddition chemistry 030220 oncology & carcinogenesis Click chemistry |
| Zdroj: | Steroids. 151:108460 |
| ISSN: | 0039-128X |
| DOI: | 10.1016/j.steroids.2019.108460 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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