Agarwal Devesh S, Anantaraju Hasitha Shilpa, Sriram Dharmarajan, Yogeeswari Perumal, Nanjegowda Shankara H, Mallu P, Sakhuja Rajeev
Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.
Drug Discovery Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad 500078, India.
Steroids. 2016 Mar;107:87-97. doi: 10.1016/j.steroids.2015.12.022. Epub 2015 Dec 31.
A series of bile acid (Cholic acid and Deoxycholic acid) aryl/heteroaryl amides linked via α-amino acid were synthesized and tested against 3 human cancer cell-lines (HT29, MDAMB231, U87MG) and 1 human normal cell line (HEK293T). Some of the conjugates showed promising results to be new anticancer agents with good in vitro results. More specifically, Cholic acid derivatives 6a (1.35 μM), 6c (1.41 μM) and 6m (4.52 μM) possessing phenyl, benzothiazole and 4-methylphenyl groups showed fairly good activity against the breast cancer cell line with respect to Cisplatin (7.21 μM) and comparable with respect to Doxorubicin (1 μM), while 6e (2.49μM), 6i (2.46 μM) and 6m (1.62 μM) showed better activity against glioblastoma cancer cell line with respect to both Cisplatin (2.60 μM) and Doxorubicin (3.78 μM) drugs used as standards. Greater than 65% of the compounds were found to be safer on human normal cell line.
合成了一系列通过α-氨基酸连接的胆汁酸（胆酸和脱氧胆酸）芳基/杂芳基酰胺，并针对3种人类癌细胞系（HT29、MDAMB231、U87MG）和1种人类正常细胞系（HEK293T）进行了测试。一些缀合物显示出有望成为具有良好体外结果的新型抗癌剂。更具体地说，具有苯基、苯并噻唑和4-甲基苯基的胆酸衍生物6a（1.35μM）、6c（1.41μM）和6m（4.52μM）对乳腺癌细胞系表现出相当好的活性，相对于顺铂（7.21μM）而言，并且相对于多柔比星（1μM）具有可比性，而6e（2.49μM）、6i（2.46μM）和6m（1.62μM）相对于用作标准的顺铂（2.60μM）和多柔比星（3.78μM）药物，对胶质母细胞瘤癌细胞系表现出更好的活性。发现超过65%的化合物对人类正常细胞系更安全。
