Three new sesquiterpenoids (1- 3) with a dihydro-beta-agarofuran skeleton were isolated from Celastrus vulcanicola. Their structures were elucidated on the basis of spectroscopic analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC, and HMBC), and the absolute configurations were determined by circular dichroism and chemical correlations. Their effects on photosynthesis were tested. Sesquiterpene 1 (50 microM) inhibits both light-dependent synthesis of ATP and the electron flow in chloroplasts, whereas at high concentrations the electron flow inhibition was partially reversed. Therefore, 1 behaves as a Hill reaction inhibitor and a weak energy transfer inhibitor and has two targets of interaction: one located at the oxygen-evolving complex, and the other located at the light-activated Mg (2+)-ATPase. Compound 2 was inactive, whereas 3 acts with the same mechanisms as 1 but was less active. Celastrus vulcanicola J. Donnell Smith (Celastraceae) is a subtropical woody vine distributed in Central America and the Caribbean. Its chemical constituents and biological activity have not yet been investigated.

P-Glycoprotein (Pgp) overexpression is one factor contributing to multidrug resistance (MDR) in cancer cells and represents one drawback in the treatment of cancer. In an attempt to find more specific and less toxic anticancer MDR-reversal agents, we report herein the isolation, structure elucidation and biological activity of nine new (, and ) and seven known (, and ) dihydro-beta-agarofuran sesquiterpenes from the leaves of Celastrus vulcanicola. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, CD studies and biogenetic means. All the compounds were assayed on human MDR1-transfected NIH-3T3 cells, in order to determine their ability to reverse the MDR phenotype due to Pgp overexpression. Six compounds from these series (, , , , and ) showed an effectiveness that was similar to (or higher than) the classical Pgp reversal agent verapamil for the reversal of resistance to daunomycin and vinblastine. The structure-activity relationships are discussed.

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