Esters of betulin and betulinic acid with amino acids have improved water solubility and are selectively cytotoxic toward cancer cells

Abstract

Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. Unfortunately they are practically insoluble in aqueous media and therefore their overall absorption index is not satisfactory. We have modified structures of both compounds by simple transformation to mono- and disubstituted esters of l-amino acids. This allowed us to achieve better water solubility without loss of the observed earlier anticancer properties. Comet assay on various cancer cell lines demonstrate that these compounds act via an apoptotic mechanism.