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Synthesis and evaluation of new macrocyclic compounds based on jatrophane scaffold

Objective

Abstract
Jatrophane are natural compounds isolated from Euphorbia (Euphorbiaceae, spurge family). More than 150 jathrophane have been isolated so far. The general structure is an highly functionalized trans-bicyclo[10.3.0]pentadecane skeleton. Jatrophanes possess a variety of different biological activities such as inhibitory activity on the mammalian mitochondrial respiratory chain, cell cleavage arrest, cytotoxicity against various human cancer cell lines, antiviral activity, antiplasmodial activity, microtubule interaction and cytotoxicity against human cancer cell lines. Most notably, they are inhibitors of the P-glycoprotein (Pgp), a membrane protein whose major function is the active transport of amphiphatic xenotoxins out of the cytoplasm. The over expression of the multi-drug resistance protein 1 (MDR1) gene (which encode for Pgp) contributes to the resistance of cancer cells against a large spectrum of anticancer drugs. Only natural occurring jatrophane have been investigated as modulator of multidrug resistance so far. Despite the large number of jatrophane isolated and the promising biological properties, the preparation this class of compounds can be regarded as a synthetic and biological challenge. The fellow has already an excellent background in synthetic chemistry. This project will allow him to increase his experience and knowledge in natural products chemistry, carbohydrate chemistry, development of bioactive compounds as well as enhance his synthetic experience. He proposes to join NUI Galway which is strategically developing strength in Biomedical Research, Cancer and Glycoscience, thus helping an objective 1 region of Europe to develop its research programme. NUI GAlway will also offer a series of transferrable skills and personal development courses to Dr. Lo Re. Both the scientific and personal training will contribute to the maturing of Dr. Lo Re to becoming an independent researcher.

Call for proposal

FP7-PEOPLE-2011-IEF
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Coordinator

NATIONAL UNIVERSITY OF IRELAND GALWAY
Address
University Road
H91 Galway
Ireland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 191 938,20
Administrative Contact
Mari Vahey (Ms.)