Clerodane diterpenes from Casearia arguta that act as synergistic TRAIL sensitizers

Abstract

Casearia arguta was investigated as part of the ongoing search for synergistic TRAIL (tumor necrosis factor-α-related apoptosis-inducing ligand) sensitizers. As a result of this study, argutins A-H, eight new highly oxygenated clerodane diterpenes, were isolated from the plant Casearia arguta collected in Guatemala. The modified Mosher ester method was utilized to establish the absolute configuration of argutins A and F. Each of the argutins showed varying levels of synergy with TRAIL. Argutin B showed the highest TRAIL sensitization; the synergistic effect of argutin B and TRAIL together was 3-fold greater than argutin B alone.

Figure 1

Key ROE correlations supporting the configuration of argutin A (1).

Figure 2

Δδ^SR values (Δδ^SR = δ^S – δ^R) for the MTPA esters 1S and 1R.

Figure 3

Δδ^SR values (Δδ^SR = δ^S – δ^R) for the MTPA esters 9S and 9R.