Synthesis and in Vitro Antiproliferative Evaluation of Some B-norcholesteryl Benzimidazole and Benzothiazole Derivatives

• Main Authors: Jianguo Cui, Binbin Qi, Chunfang Gan, Zhipin Liu, Hu Huang, Qifu Lin, Dandan Zhao, Yanmin Huang
• Format: Article
• Language: English
• Published: MDPI AG 2015-04-01
• Series: Marine Drugs
• Subjects: cholesterol; B-norcholesteryl benzimidazoles; B-norcholesteryl benzothiazoles; antiproliferative activity; apoptosis
• Online Access: http://www.mdpi.com/1660-3397/13/4/2488

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.