Jatrophane Diterpenes as P-Glycoprotein Inhibitors. First Insights of Structure−Activity Relationships and Discovery of a New, Powerful Lead

The Mediterranean spurge Euphorbia dendroides L. afforded a series of 10 closely related jatrophane polyesters, nine of which are new, which served as a base for the establishment of structure−activity relationships within this class of P-glycoprotein inhibitors. The results, while pointing to the g...

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Published in:Journal of medicinal chemistry 2003-07, Vol.46 (15), p.3395-3402
Main Authors: Corea, Gabriella, Fattorusso, Ernesto, Lanzotti, Virginia, Taglialatela-Scafati, Orazio, Appendino, Giovanni, Ballero, Mauro, Simon, Pierre-Noël, Dumontet, Charles, Di Pietro, Attilio
Format: Article
Language:English
Subjects:
ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors
ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry
Biochemistry, Molecular Biology
Biological and medical sciences
Diterpenes - chemistry
Diterpenes - isolation & purification
Euphorbia - chemistry
General pharmacology
Life Sciences
Medical sciences
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Protein Binding
Structure-Activity Relationship
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cited_by cdi_FETCH-LOGICAL-a413t-80b2bd7181a7d9bae672f3bf5f5ecffc896105402c708c397db6f9c38bbdec013
cites cdi_FETCH-LOGICAL-a413t-80b2bd7181a7d9bae672f3bf5f5ecffc896105402c708c397db6f9c38bbdec013
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container_issue 15
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container_title Journal of medicinal chemistry
container_volume 46
creator Corea, Gabriella
Fattorusso, Ernesto
Lanzotti, Virginia
Taglialatela-Scafati, Orazio
Appendino, Giovanni
Ballero, Mauro
Simon, Pierre-Noël
Dumontet, Charles
Di Pietro, Attilio
description The Mediterranean spurge Euphorbia dendroides L. afforded a series of 10 closely related jatrophane polyesters, nine of which are new, which served as a base for the establishment of structure−activity relationships within this class of P-glycoprotein inhibitors. The results, while pointing to the general role of lipophilicity for activity, also highlighted the relevance of the substitution pattern at the positions 2, 3, and 5, suggesting the involvement of this fragment in binding. The most powerful compound of the series, euphodendroidin D (4), outperformed cyclosporin by a factor of 2 to inhibit Pgp-mediated daunomycin transport.
doi_str_mv 10.1021/jm030787e
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subjects ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors
ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry
Biochemistry, Molecular Biology
Biological and medical sciences
Diterpenes - chemistry
Diterpenes - isolation & purification
Euphorbia - chemistry
General pharmacology
Life Sciences
Medical sciences
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Protein Binding
Structure-Activity Relationship
title Jatrophane Diterpenes as P-Glycoprotein Inhibitors. First Insights of Structure−Activity Relationships and Discovery of a New, Powerful Lead
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