Unit:
Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική ΒιομηχανίαLibrary of the School of Science
Supervisors info:
Γεώργιος Κόκοτος Καθηγητής ΕΚΠΑ (Επιβλέπων), Παναγιώτα Μουτεβέλη-Μηνακάκη Καθηγήτρια ΕΚΠΑ, Σταματία Βασιλείου Λέκτορας ΕΚΠΑ
Original Title:
Φωσφονικοί και φωσφινικοί αναστολείς της αυτοταξίνης
Translated title:
Phosphonates and Phosphinic Inhibitors of Autotaxin
Summary:
Autotaxin (ATX) posseses lysophospholipase D activity, catalyzing the
hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA), and it
is considered the primary LPA-producing enzyme in the circulation. LPA is a
bioactive phospholipid which stimulates various cellular functions, including
migration and proliferation. LPA is actively involved in chronic inflammatory
disorders and cancer. Therefore, direct inhibition of ATX could regulate the
production of LPA, against various pathophysiological conditions.
In this thesis, we synthesized phosphonates and optically active amino
phosphinic acids containing amide or thioamide bonds, as inhibitors of ATX. To
this end, initially, we studied the synthesis of optically active amino
phosphinic acids obtained from protected amino acids.
The strong binding which phosphonates and phosphinic acids may present in the
active side of ATX, combined with the stability of P-C bond in hydrolytic
cleaving and the selectivity offered by optical purity, make these compounds
important for the development of potent and selective inhibitors. Phosphinic
derivatives based on δ-amino phosphinic acids were found to exhibit potent
inhibitory activity against autotoxin.
Keywords:
Autotaxin, Inhibitor, Phosphonates, Phosphinic acids, Amino acids
Number of index pages:
1-7
Number of references:
165
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