The synthesis and antitumor activity of lithocholic acid and its derivatives

• Published in: Steroids 2017-09, Vol.125, p.54-60
• Main Authors: He, Xiao-Long, Xing, Yajing, Gu, Xiang-Zhong, Xiao, Jie-Xin, Wang, Ying-Ying, Yi, Zhengfang, Qiu, Wen-Wei
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor; Apoptosis; Apoptosis - drug effects; Breast cancer; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemistry Techniques, Synthetic; Drug Screening Assays, Antitumor; Humans; Lithocholic acid; Lithocholic Acid - chemical synthesis; Lithocholic Acid - chemistry; Lithocholic Acid - pharmacology; MCF-7 Cells; Migration; Structure-Activity Relationship
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2017.06.009

A concise synthesis of lithocholic acid and its amide derivatives and evaluation of their activity against the growth of breast cancer cell lines. [Display omitted] •A concise synthesis of lithocholic acid and its amide derivatives was reported.•The antiproliferative activities of these derivatives were evaluated in vitro.•Transwell migration, colony formation and apoptosis assays were performed. In this paper, a new and concise synthetic route of lithocholic acid (LCA) using commercially available steroid source deoxycholic acid is reported. A series of amide derivatives of LCA were also synthesized and investigated for their activity against the growth of MCF-7 and MCF-7/ADR cells using the sulforhodamine B assay. For MCF-7, the most potent compound 20 showed a 20-fold higher antitumor activity than LCA. For MCF-7/ADR, the most potent compound 24 showed a 22-fold higher antitumor activity than LCA. The transwell migration assay of 20 was evaluated on MDA-MB-231 cells. The colony formation and apoptosis assays of 20 were performed on MCF-7 and MCF-7/ADR cell lines.