Abstract：
:From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed the importance of substitutions on the medium-sized ring (carbons 8, 9, 14, and 15). In particular, the activity is collapsed by the presence of a free hydroxyl at C-8, while it increases with a carbonyl at C-14, an acetoxyl at C-9, and a free hydroxyl at C-15. The most potent compound of the series, pepluanin A, showed a very high activity for a jatrophane diterpene, outperforming cyclosporin A by a factor of at least 2 in the inhibition of Pgp-mediated daunomycin transport.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Corea G,Fattorusso E,Lanzotti V,Motti R,Simon PN,Dumontet C,Di Pietro Adoi
10.1021/jm030951ykeywords:
subject
Has Abstractpub_date
2004-02-12 00:00:00pages
988-92issue
4eissn
0022-2623issn
1520-4804journal_volume
47pub_type
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