Amino Acid Conjugates of ent-Beyerane-type Diterpenoids and Oleanane-type Triterpenoids: Synthesis and Evaluation of Cytotoxic Activities

Abstract

The aim of this study was to increase the cytotoxic activities of terpenoids via amino acid conjugation. Thus, 21 new ester derivatives (5-15, 19-27, and 29) were prepared by conjugation of the hydroxy groups in ent-beyerane-type diterpenoids (4) and oleanane-type triterpenoids (18), and their cytotoxic activity against three human cancer cell lines (leukemia, lung, and stomach) were evaluated. The prepared compounds showed cytotoxic effects; in particular, all amino acid conjugates of ent-beyerane-type diterpenoids (5-13) exhibited potent cytotoxic activity (IC₅₀ 1.0-3.7 µM for HL60, 1.7-8.2 µM for A549, and 2.5-11.7 µM for MKN45). In addition, no differences were observed in the cytotoxic activities of l- and d-type amino acid conjugates.

graphical abstract