Lathyrane diterpenes from Euphorbia lathyris as modulators of multidrug resistance and their crystal structures

Two lathyrane diterpenes (1–2) together with previous ones (3–6) were isolated from Euphorbia lathyris. The structures of 1 and 2 were established on the basis of extensive spectroscopic methods, including two-dimensional NMR techniques. Stereo configuration and conformation of 1 and 2 were analyzed by X-ray diffraction for the first time. The configuration of the unique isolathyrol diterpene 2 from the seeds of E. Lathyris, was rectified from S∗ to R∗ at C-5. All compounds were examined as modulators of multidrug resistance on MCF-7/ADM cell lines in vitro. Their structure–activity relationship was discussed from aspect of different skeletons. A class of potential P-gp inhibitors with five different types (jokinol, isolathyrol, epoxylathyrol, 7-hydroxylathyrol, lathyrol) was discovered.

Two lathyrane diterpenes Euphorbia factor L7a (1) and Euphorbia factor L7b (2) together with four previous ones were isolated from Euphorbia lathyris. The structures of 1 and 2 were established on the basis of extensive spectroscopic methods, including two-dimensional NMR techniques. Stereo configuration and conformation of 1 and 2 were analyzed by X-ray diffraction for the first time. The configuration of the diterpene 2 was rectified from S∗ to R∗ at C-5. A class of potent P-gp inhibitors with five different types: jokinol, isolathyrol, 7-hydroxylathyrol, epoxylathyrol, lathyrol was discovered from this Chinese traditional medicine. Their structure–activity relationship was elucidated from aspect of skeletons.Figure optionsDownload as PowerPoint slide