Clerodane diterpenes from Casearia arguta that act as synergistic TRAIL sensitizers.
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.
Molecular Targets Laboratory, Molecular Discovery Program, Center for Cancer Research, NCI-Frederick, Frederick, MD 21702, USA.
Emily L
EL
Whitson
Cheryl L
CL
Thomas
Curtis J
CJ
Henrich
Thomas J
TJ
Sayers
James B
JB
McMahon
Tawnya C
TC
McKee
D037821:Casearia / Q000737:chemistry*; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006166:Guatemala; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects*
D045785:Diterpenes, Clerodane; D053221:TNF-Related Apoptosis-Inducing Ligand; C555184:argutin B