苯并咪唑基取代的甾体衍生物合成

Synthesis and Antiproliferative Activities of Some Novel Steroidal Compounds with Benzimidazole Groups

摘要:

以孕烯醇酮为原料，通过对孕烯醇酮的C-17 '支链进行化学修饰，设计合成了18个甾核的C-17 '-支链为苯并咪唑基取代的甾体化合物，通过IR、1H NMR、13C NMR和HRMS 对化合物进行了结构表征，采用溴化噻唑蓝四氮唑(MTT)法测试了这些化合物对人口腔上皮癌细胞(KB)、宫颈癌细胞(HeLa)、人肝癌细胞(HepG)、人鼻咽癌细胞(CNE-2)、乳腺癌细胞(BT474)、卵巢癌细胞(SKOV3)的体外抑制活性。结果表明，部分化合物具有中等程度的活性，其中氟基取代的苯并咪唑甾体化合物5c和6c对人体卵巢癌细胞(SKOV3)具有良好的选择性抑制作用，IC50 (半抑制浓度)值分别为(15.4±3.8)和(9.2±0.5)μmol/L。该类化合物可为设计开发新型抗肿瘤药物提供参考。

Abstract:

Using pregnenolone as starting material, 16 steroidal derivatives Using pregnenolone as starting material, 16 steroidal derivatives containing benzimidazole heterocycle were designed and synthesized by suitable modification at C17 side chain of pregnenolone, their structures were characterized by IR, 1H NMR、13C NMR and HRMS. The antiproliferative activity of the target compounds in vitro was evaluated against KB, HeLa, HepG, CNE-2, BT474 and SKOV3 cancer cells by MTT method. The results show that some compounds possess distinct antiproliferative activities against tested cells. Among the active compounds, compound 5c and 6c show better selective activities against SKOV3 cells with IC50 values of 15.4±3.8 and 9.2±0.5 μmol/L, respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.