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.
Jiao
Wei
W
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China. jw2272001@yahoo.com.cn
Dong
Weiwei
W
Li
Zhefeng
Z
Deng
Meicai
M
Lu
Runhua
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D028481:Euphorbia / Q000737:chemistry*; D005260:Female; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes; C530347:lathyrane