Synthesis and Cytotoxic Activity of Friedelinyl Esters

Commonly isolated from plants of Celastraceae family, pentacyclic triterpenoids have a broad spectrum of biological activities, such as antitumor, anti-inflammatory, antinociceptive properties, among others. Structural modifications in these triterpenoids can enhance their biological activity, as well as their selectivity, while improving their physicochemical and pharmacokinetic aspects. In this study, eight novel esters were synthesized: four derivatives of 3 alpha-friedelinol (friedelan-3 alpha-yl p-bromobenzoate (1a); friedelan-3 alpha-yl naproxenate (1b); friedelan-3 alpha-yl pent-4-ynoate (1c); friedelan-3 alpha-yl undec-10-ynoate (1d)) and four derivatives of 3 beta-friedelinol (friedelan-3 beta-yl p-bromobenzoate (2a); friedelan-3 beta-yl naproxenate (2b); friedelan-3 beta-yl pent-4-ynoate (2c); friedelan-3 beta-yl undec-10-ynoate (2d)). Overall, 3 alpha-friedelinol showed greater reactivity when compared to the beta-epimer. The esters 1b-d and 2b-c were tested for antileukemic activity against THP-1 and K-562 cells but showed low cytotoxicity for both cell lines. The most active against THP-1 cells was friedelan-3 beta-yl naproxenate (2b, IC50=266 +/- 6 mu M), and the most active against K-562 cells was friedelan-3 alpha-yl pent-4-ynoate (1c, IC50=267 +/- 5 mu M). image