Cui Jianguo, Qi Binbin, Gan Chunfang, Liu Zhipin, Huang Hu, Lin Qifu, Zhao Dandan, Huang Yanmin
College of Chemistry and Material Science, Guangxi Teachers Education University, Nanning 530001, China.
Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Qizhou University, Qizhou 535099, China.
Mar Drugs. 2015 Apr 22;13(4):2488-504. doi: 10.3390/md13042488.
Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T) was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3β'-Acetoxy-5β'-hydroxy-6'-B-norcholesteryl)benzimidazole (9b) with the structure of 6-benzimidazole displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T). The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.
以口山甾醇（一种源自日本海海绵希瓦氏星骨海绵的化合物）为先导化合物，合成了一些新型的β-降胆固醇基苯并咪唑和苯并噻唑衍生物。测定了这些化合物对人宫颈癌（HeLa）、人肺癌（A549）、人肝癌细胞（HEPG2）和正常肾上皮细胞（HEK293T）的抗增殖活性。结果表明，对于提高化合物的抗增殖活性而言，苯并咪唑基团是比苯并噻唑基团更好的取代基。具有6-苯并咪唑结构的2-(3β'-乙酰氧基-5β'-羟基-6'-β-降胆固醇基)苯并咪唑（9b）在所有化合物中对癌细胞表现出最佳的抗增殖活性，但对正常肾上皮细胞（HEK293T）几乎无活性。通过流式细胞术对化合物9b诱导癌细胞凋亡的测定表明，该化合物能够有效诱导癌细胞凋亡。该研究为新型抗癌药物的探索提供了理论参考，可能有助于新型化疗药物的设计。
