Supervisors info:
Γεώργιος Κόκοτος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Summary:
Recently, there has been high interest in the discovery of new anti-inflammatory drugs which, unlike existing non-steroidal anti-inflammatory drugs, would present a new mechanism of action and would, as far as possible, be deprived of gastrointestinal and cardiovascular side effects. In addition, the potential protection that anti-inflammatory drugs may provide against certain types of cancer has come to light.
As a result, in addition to cyclooxygenase-2 (COX-2) inhibitors, phospholipases A2 (PLA2) and microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have been designed and synthesized in recent years, in an effort to find new means to combat inflammatory conditions.
Recently, in the Laboratory of Organic Chemistry of the University of Athens, several synthetic inhibitors of PGE2 production have been developed, including inhibitors of various PLA2 subclasses. Compounds based on a 2-aminobenzothiazole backbone, containing a naphthalene ring, have been found to exhibit strong inhibition of PGE2 production at cellular level.
In the present thesis, the aim was to synthesize new inhibitors of PGE2 production in order to study their structure-activity relationship as anti-inflammatory agents. In particular, compounds were synthesized to study the substitution position of the naphthalene ring, the reduction of lipophilicity and the role of the benzothiazole ring. Also, the compounds synthesized have been studied for their cytotoxicity against diverse cell lines.