Synthesis and cytotoxicity of A-homo-lactam derivatives of cholic acid and 7-deoxycholic acid

Using cholic acid and deoxycholic acid as starting materials, a series of 3-aza-A-homo-4-one bile acid and 7-deoxycholic acid derivatives were synthesized by the esterification, oxidation, reduction, oximation and Beckman rearrangement etc. The cytotoxicity of the synthesized compounds against MGC 7901 (human ventriculi carcinoma cell line), hela (human cervical carcinoma cell line), SMMC 7404 (human liver carcinoma cell line) were investigated. The results showed that bile acid and 7-deoxycholic-acid derivatives with 3-aza-A-homo-4-one configuration bearing a 6-hydroximino or 12-hydroximino group displayed a distinct cytotoxicity to Hela tumor cell line. In particular, the IC50 values of the compounds 6 and 13 were 14.3 and 24.3  μmol/L against Hela human tumor cell line respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.

► A new series of A-homo-lactam derivatives of cholic acid and 7-deoxycholic acid have been synthesized and characterized. ► The results showed that the bile acid and 7-deoxycholic-acid derivatives bearing a 6-hydroximino or 12-hydroximino group displayed a distinct cytotoxicity to Hela tumor cell line and the compounds with A-homo-lactam structure have a better cytotoxicity than corresponding steroidal oxime compounds. The methyl 4,12-dioxo-7-hydroxyimino-3-aza-A-homo-cholicate(6) displayed a better cytotoxicity than the cisplatin to Hela tumor cell line. ► Findings could provide new evidence showing the relationship between the chemical structure and biological activity and may be useful for the design of novel chemotherapeutic drugs.