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

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.