Unit:
Κατεύθυνση Οργανική ΧημείαLibrary of the School of Science
Supervisors info:
Θ. Μαυρομούστακος Καθηγητής ΕΚΠΑ (επιβλέπων), Γ. Κόκοτος Καθηγητής ΕΚΠΑ, Β. Μαγκριώτη Λέκτορας ΕΚΠΑ
Original Title:
Δημιουργία φαρμακοφόρου μοντέλου για το ένζυμο της κυτοσολικής φωσφολιπάσης Α2. Χρήση βιβλιοθηκών για την εξεύρεση χημικών οργανικών ενώσεων με υψηλή βαθμονόμηση μοριακής πρόσδεσης
Translated title:
Creation of pharmacophore model for the enzyme cytosolic phospholipase A2 (cPLA2). The use of chemical databases for the discovery of novel potential leads.
Summary:
The fundamental function of enzyme cytosolic phospholipase A2 (cPLA2) is to
release arachidonic acid from the phospholipid membranes. Arachidonic acid is
the precursor for the formation of lipid mediators of inflammation, including
eicosanoids. Therefore, the enzyme is an interesting target for biochemical and
structural studies which can lead to a deeper knowledge of the treatment of
inflammation. In the first part of this thesis, the creation of a complex of
the enzyme and the inhibitor AX074 is described by the Induced Fit methodology.
AX074 presents the strongest biological activity of the 2-oxoamide inhibitors
that have been synthesized by the group of Professor George Kokotos in the
Laboratory of Organic Chemistry of University of Athens. In the second part of
this thesis, a pharmacophore model has been created based on the Ligand-Based
methodology and the process of «Pharmacophore-Based Virtual Screening (VS)» has
been applied to commercially available compound libraries. For «hits» compounds
that emerged from this process, molecular docking experiments have been
performed in order to investigate their docking scoring.
Keywords:
Human Cytosolic Phospholipases A2, Induced Fit, Pharmacophore Model, Pharmacophore-Based Virtual Screening, Hits
Number of index pages:
19-27, 29-32
