Synergistic TRAIL sensitizers from Barleria alluaudii and Diospyros maritima.
Barleria alluaudii and Diospyros maritima were both investigated as part of an ongoing search for synergistic TRAIL (tumor necrosis factor-α-related apoptosis-inducing ligand) sensitizers. As a result of this study, two naphthoquinone epoxides, 2,3-epoxy-2,3-dihydrolapachol (1) and 2,3-epoxy-2,3-dihydro-8-hydroxylapachol (2), both not previously isolated from natural sources, and the known 2-methylanthraquinone (3) were identified from B. alluaudii. Time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra were utilized to establish the absolute configuration of 1 and 2. Additionally, five known naphthoquinone derivatives, maritinone (4), elliptinone (5), plumbagin (6), (+)-cis-isoshinanolone (7), and ethylidene-6,6'-biplumbagin (8), were isolated from D. maritima. Compounds 1, 2, and 4-6 showed varying levels of synergy with TRAIL. Maritinone (4) and elliptinone (5) showed the highest synergistic effect, with more than a 3-fold increase in activity observed with TRAIL than with compound alone.
Molecular Targets Laboratory, Molecular Discovery Program, Center for Cancer Research, NCI-Frederick, Frederick, Maryland 21702, United States.
Emily L
EL
Whitson
Han
H
Sun
Cheryl L
CL
Thomas
Curtis J
CJ
Henrich
Thomas J
TJ
Sayers
James B
JB
McMahon
Christian
C
Griesinger
Tawnya C
TC
McKee
D027901:Acanthaceae / Q000737:chemistry*; D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D029788:Diospyros / Q000737:chemistry*; D008270:Madagascar; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha
D000880:Anthraquinones; D009285:Naphthoquinones; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; C489087:maritinone; C073955:2-methylanthraquinone; C014758:plumbagin