Synthesis of cholesteryl doxorubicin and its anti-cancer activity

Doxorubicin (dox) has been used as anti-cancer agent, but there are disadvantages such as rapid excretion, short retention time and cardiotoxicity. For giving lipophilic properties to dox, it was modified with cholesterol derivatives that were validated as a component of liposomal gene delivery. This article describes the synthesis of dox derivatives (lipo-dox A-D), their cytotoxicity and cellular uptake. In A549, HeLa, MCF7 and MDA MB 231 cell lines, lipo-dox A and lipo-dox B substituted at alcohol group showed similar anti-cancer effect as dox, but lipo-dox C and lipo-dox D substituted at amino group did not. As a result, the amino group of dox seems an important site for its cancer cell inhibition. Lipophilic property of lipo-dox A and lipo-dox B induced more accumulation in cells compared to parent drug. Therefore, the newly synthesized lipo-dox A and lipo-dox B would be a good candidate for anti-cancer agent.