Unit:
Department of ChemistryLibrary of the School of Science
Author:
Gerokonstantis Triantafyllos-Dimitrios
Dissertation committee:
Παναγιώτα Μηνακάκη- Μουτεβελή, Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Γεώργιος Κόκοτος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Σταματία Βασιλείου, Επίκουρος Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Θωμάς Μαυρομούστακος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Αθανάσιος Γκιμήσης, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Δημήτριος Γεωργιάδης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Βικτωρία Μαγκριώτη, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Original Title:
Σύνθεση αμιδικών παραγώγων φυσικών αμινοξέων και αναλόγων τους και μελέτη των παραγώγων αυτών ως εν δυνάμει αναστολέων της αυτοταξίνης
Translated title:
Αγγλικά
Summary:
Autotaxin (ATX), a glycoprotein (~ 125 kDa) isolated as an autocrine motility factor from melanoma cells, belongs to a seven-membered family of ectonucleotide pyrophosphatase / phosphodiesterase (ENPP), and exhibits lysophospholipase D activity. ATX is responsible for the hydrolysis of lysophosphatidylcholine (LPC) to produce the bioactive lipid lysophosphatidic acid (LPA), which is upregulated in a variety of pathological inflammatory conditions, including fibrosis, cancer, liver toxicity, thrombosis etc. Given its role in human disease, the ATX-LPA axis is an interesting target for therapy, and the development of novel potent ATX inhibitors is of great importance. In the present work a novel class of ATX inhibitors, optically active derivatives of 2-pyrrolidinone and pyrrolidine heterocycles were synthesized. Some of them exhibited interesting in vitro activity, namely the hydroxamic acid 7 (IC50 700 nM), while the boronic acid derivatives 4α (IC50 50 nM), 4β (IC50 120 nM), 4γ (IC50 180 nM) and 4 (IC50 35 nM) were found to be potent inhibitors of ATX.
Main subject category:
Science
Keywords:
Autotaxin, Inhibitors, Lysophosphatidic acid, 2-Pyrrolidinone, Pyrrolidine
Number of references:
278
