Esters and amides of maslinic acid trigger apoptosis in human tumor cells and alter their mode of action with respect to the substitution pattern at C-28.

Cancer is one of the most commonly diagnosed diseases worldwide; its mortality rate is high, and there is still a demand for the development of antitumor active drugs. Triterpenoic acids show many pharmacological effects, among them antitumor activity. One of these, maslinic acid-1 is of interest because of its antitumor profile. It is not only cytotoxic but also triggers apoptosis in various human tumor cell lines. To improve the cytotoxicity of parent 1 we set out to synthesize a series of esters and amides differing in structure and lipophilicity. These compounds were tested in a sulforhodamine B assay for cytotoxicity, and screened for their ability to induce apoptosis using an acridine orange/propidium iodide assay, DNA laddering and cell cycle experiments. Esters containing small-chain, lipophilic residues increased the cytotoxicity whereas amides as well long-chain esters led to a decrease in activity. The antitumor activity seems to be independent from the substitution pattern at position C-28 for esters and amides but alters their mode of action.