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Synergistic TRAIL sensitizers from Barleria alluaudii and Diospyros maritima

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45



* FARE Award Winner


  • E. L. Whitson
  • H. Sun
  • C. L. Thomas
  • C. J. Henrich
  • T. J. Sayers
  • J. B. McMahon
  • K. R. Gustafson
  • C. Griesinger
  • T. C. McKee


A high-throughput screen was developed to identify compounds that could sensitize tumor cells to the killing effects of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL). Extracts from Barleria alluaudii and Diospyros maritima showed promising activity in the initial screen and were further investigated. 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-methyl anthraquinone (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 three-fold increase in activity observed with TRAIL than with compound alone.

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