Abstract
The macrocyclic lathyrane diterpene latilagascene B, previously isolated from Euphorbia lagascae, was acylated to afford three new diterpene esters, latilagascenes G ( 1), H ( 2), and I ( 3), whose structures were assigned by spectroscopic methods. These acyl derivatives, and the macrocyclic diterpenes of the jatrophane-type, tuckeyanols A ( 4) and B ( 5), and euphotuckeyanol ( 6), isolated from Euphorbia tuckeyana, were tested for P-gp modulating properties on human MDR1 gene-transfected and parental L5178 mouse lymphoma cell lines. All the compounds displayed very strong activity. The molecular orbital energies (HOMO and LUMO) of diterpenes 1– 6 and 7– 13, previously isolated, have also been calculated in order to estimate their probable charge transfer interactions with P-gp. Structure–activity relationships (SAR) are discussed. Furthermore, compounds ( 1– 6) were assayed, in vitro, for their antiproliferative effects in combination with epirubicine and all of them synergistically enhance the effect of the antitumor drug.
Published Version
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