Synthesis and antiproliferative activity of C-homo-lactam derivatives of 7-deoxycholic acid

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 7; pp. 2265 - 2267
• Main Authors: Huang, Yanmin, Cui, Jianguo, Chen, Sijing, Gan, Chunfang, Yao, Qiucui, Lin, Qifu
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2013
• Subjects: 12-Oxy-12a-aza-C-homo-7-deoxycholic acid derivatives; 7-Deoxycholic acid; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; C-homo-lactam; Cell Line, Tumor; Cell Proliferation - drug effects; Cytotoxicity; Deoxycholic Acid - chemical synthesis; Deoxycholic Acid - chemistry; Deoxycholic Acid - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Lactams - chemistry; Molecular Structure; Structure-Activity Relationship; 7-Deoxycholic acid; C-homo-lactam; Cytotoxicity; 12-Oxy-12a-aza-C-homo-7-deoxycholic acid derivatives; Antiproliferative activity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.08.064

A series of 12a-aza-C-homo-12-one 7-deoxycholic acid derivatives were synthesized and their antiproliferative activities were assayed. The IC50 values of the compounds 6 and 7 against Tu 686 cells are 16.7 and 19.8μM/L, respectively.
Using deoxycholic acid as starting materials, a series of 12a-aza-C-homo-12-one 7-deoxycholic acid derivatives were synthesized The antiproliferative activity of the synthesized compounds against some carcinoma cell lines was investigated. The results showed that some 12-oxy-12a-aza-C-homo-7-deoxycholic acid derivatives displayed distinct cytotoxicity to HeLa (human cervical carcinoma) and Tu 686 (laryngocarcinoma) tumor cell lines. In particular, the IC50 values of the compounds 6 and 7 against Tu 686 cells are 16.7 and 19.8μM/L respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.