Jatrophane Diterpenes from Euphorbia esula as Antiproliferative Agents and Potent Chemosensitizers to Overcome Multidrug Resistance

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Abstract
Phytochemical study of whole, undried plants of Euphorbia esula led to the isolation of six new (1–6) jatrophane diterpene polyesters, named esulatins H–M, together with the known compounds 2α,3β,5α,7β,15β-pentaacetoxy-9α-nicotinoyloxyjatropha-6(17),11-dien-14-one (7), salicinolide (8), and euphosalicin (9). The structures and relative configuration of 1–6 were established on the basis of extensive spectroscopic analysis, including HRESIMS and one- and two-dimensional NMR techniques. All these compounds, together with diterpenes (10–14) isolated previously from this plant, were evaluated for their antiproliferative activity against HeLa, Ishikawa, and MCF7 cells. The multidrug-resistance-reversing activities were also investigated on L5178 mouse lymphoma cells transfected with the pHa MDR1/A retrovirus DNA. Preliminary structure–activity relationship data are discussed.

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