Hydroxyethylamide substituted triterpenoic acids hold good cytotoxicity for human tumor cells

Abstract

Pentacyclic triterpenoic acids, betulinic acid, platanic acid, oleanolic acid and ursolic acid, were acetylated and subsequently converted into mono-, bis- and tris(hydroxyl)ethyl amides. While parent compounds are of none or minor cytotoxicity, these amides showed EC50 values even in low μM concentration for a variety of different human tumor cell lines. Especially a bis(hydroxyethyl)amide 12 derived from oleanolic acid held an EC50 = 7.7 μM for A375 melanoma cells while being less cytotoxic for non-malignant fibroblasts NIH 3 T3 (EC50 > 30 μM). Several of these amides were converted into their corresponding sulfamates. While these sulfamates held no inhibitory activity for the enzyme carbonic anhydrase II, the highest cytotoxicity was observed for a betulinic acid derived sulfamate 17 with an EC50 = 4.9 μM for A375 melanoma cells.