Unit:
Department of ChemistryLibrary of the School of Science
Author:
Ntatsopoulos Vasileios
Dissertation committee:
Σταματία Βασιλείου, Επίκουρη Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Γεώργιος Βουγιουκαλάκης, Επίκουρος Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Χριστόφορος Κόκοτος, Επίκουρος Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Δημήτριος Γεωργιάδης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Γεώργιος Κόκοτος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Θωμάς Μαυρομούστακος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Παναγιώτα Μουτεβελή-Μηνακάκη, Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Original Title:
Σχεδιασμός, σύνθεση και ενζυμικές μελέτες αναστολέων ουρεάσης
Translated title:
Design, synthesis and enzymatic studies of urease inhibitors
Summary:
In Chapter 1 of the present thesis the urease enzyme is analyzed. Its structure and its catalytic mechanism are examined, followed by ureases’ role in Αgriculture and Μedicine, along with certain groups of inhibitors. Afterwards, in Chapter 2, a literature review of phosphorus chemistry and the most significant reactions leading to P-C bond formation are presented. In the final Chapter, the synthesis of novel organophosphorus compounds as inhibitors of urease is outlined, together with a study of their inhibitory action. The aim of this study was the synthesis of phosphonic acids as potential covalent inhibitors of bacterial ureases. Phosphonomethyl-cinnamic acid 157 excibited the highest potency, with Ki=0.594 μΜ for Sporosarcina pasteurii urease and Ki=0.485 μΜ for Proteus mirabilis urease. However, compound 157 appeared reversible and competitive. Phosphonopropyl-cinnamic acid 194 was also found to be the most potent inhibitor, with Ki=0.509 μΜ for Sporosarcina pasteurii urease. The observed inhibition kinetics suggest a mixed mechanism, where covalent and noncovalnet inhibition may occur. All compounds were also assayed against Proteus mirabilis urease. Compound 194 remained the most potent derivative, with IC =11.0 m=μΜ, whilst phosphonobutyl-cinnamic acid 209 displayed the highest antimicrobial activity against Proteus mirabilis, with LC =28,6 μΜ.
Main subject category:
Science
Keywords:
Urease, Sporosarcina pasteurii, inhibitors, phosphinic acids, phosphonic acids
Number of references:
289
