新型常春藤皂苷元-三唑基衍生物作为潜在的抗癌药物。
Novel hederagenin-triazolyl derivatives as potential anti-cancer agents.
作者信息
Rodríguez-Hernández Diego, Demuner Antonio J, Barbosa Luiz C A, Heller Lucie, Csuk René
机构信息
Department of Chemistry, Universidade Federal de Viçosa, Av. P. H. Rolfs, s/n, CEP 36570-900, Viçosa, MG, Brazil; Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Campus Pampulha, CEP 31270-901, Belo Horizonte, MG, Brazil.
Department of Chemistry, Universidade Federal de Viçosa, Av. P. H. Rolfs, s/n, CEP 36570-900, Viçosa, MG, Brazil.
出版信息
Eur J Med Chem. 2016 Jun 10;115:257-67. doi: 10.1016/j.ejmech.2016.03.018. Epub 2016 Mar 9.
A series of novel aryl-1H-1,2,3-triazol-4-yl methylester and amide derivatives of the natural product hederagenin was synthesized aiming to develop new antitumor agents, using Huisgen 1,3-dipolar cycloaddition reactions, with yields between 35% and 95%. The structures of all derivatives (2-31) were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic data. The cytotoxic activities of all compounds were screened against a panel of six human cancer cell lines using SRB assay. It was found that most of the compounds displayed higher levels of antitumor activities as compared to parent hederagenin. Compounds 4, 8 and 15 were the most potent against all human cancer cell lines. Furthermore, compound 11 was the most cytotoxic against cell HT29 showing EC50 = 1.6 μM and a selectivity index of 5.4.
为了开发新型抗肿瘤药物，利用惠斯根1,3 -偶极环加成反应合成了一系列天然产物常春藤皂苷元的新型芳基 - 1H - 1,2,3 -三唑 - 4 -基甲酯和酰胺衍生物，产率在35%至95%之间。所有衍生物（2 - 31）的结构通过质谱、红外光谱、¹H核磁共振和¹³C核磁共振光谱数据得到证实。使用SRB测定法针对一组六种人类癌细胞系筛选了所有化合物的细胞毒性活性。结果发现，与母体常春藤皂苷元相比，大多数化合物表现出更高水平的抗肿瘤活性。化合物4、8和15对所有人类癌细胞系的活性最强。此外，化合物11对细胞HT29的细胞毒性最强，显示出EC50 = 1.6 μM，选择性指数为5.4。
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