Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική Βιομηχανία
Library of the School of Science

2016-03-03

2016

Κωνσταντινίδη Αθηνά

Θωμάς Μαυρομούστακος - Καθηγητής ΕΚΠΑ (επιβλέπων), Γεώργιος Κόκοτος - Καθηγητής ΕΚΠΑ, Αντώνης Κολοκούρης - Αναπληρωτής Καθηγητής ΕΚΠΑ

Μοριακή Πρόσδεση της Ένωσης ΑΧ074 στα Ένζυμα των Λιποξυγονασών, Κυκλοξυγονασών και hc-PLA2 καθώς και Παραγώγων Ασπαρτάμης στην hc-PLA2

Greek

Molecular Docking of AX074 at Lipoxygenases, Cyclooxygenases and hc-PLA2 enzymes and aspartame derivatives at hc-PLA2

In the present master thesis, the binding affinity of the GIVA-PLA2 inhibitor
AX074 over known isoforms of the enzymes cyclooxygenases and lipoxygenases has
been studied. These enzymes generate the production of chemical compounds that
have a key role in the process of signal transduction in the organism and are
involved both at pathological and at physiological responses. For example they
are involved in the initiation of a number of processes which result in the
initiation and resolution of inflammation in various diseases including asthma
and arthritis. Additionaly, were carried out comparative molecular docking
experiments with known inhibitors and the natural substrate arachidonic acid
for each isoform of these two enzymes. The AX074 binds at the in silico
experiments, using algorithm Glide, to the cyclooxygenases and to the
lipoxygenases, though to a lesser degree in comparison to the substrate
arachidonic acid according to empirical scoring. This is due to its additional
side butyl alkyl chain and the additional carbon of the 2-oxoacyl chain in its
structure. Interestingly, both the AX074 and arachidonic acid adopt a U-shaped
conformation within the active site. The results indicate that AX074 molecule
may bind favorably to cyclooxygenases and lipoxygenases.
It was also studied the de novo rational design of lipophilic derivatives of
aspartame. The in silico docking results, using algorithm Glide, showed new
molecules with a more favorable binding energy compared with aspartame and in
silico structure activity relationships were devised.

Anti-inflammatory activity, Lipophilic derivatives of aspartame, Molecular docking, Cyclooxygenase, Lipoxygenase

Yes

xv-xxii

Yes

116

xxii, 151

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https://pergamos.lib.uoa.gr/uoa/dl/object/1319110