Faculty of Veterinary Science
Department of Veterinary Anatomy and Physiology
Selected Highlights from Research Findings
For several years, the 2-arylquinolin-4(1H)-ones and their derivatives have been the subject of investigations as a new class of antitumour agents. Although the antitumour activities of quinolone derivatives are well documented, their effects on angiogenesis have not been thoroughly studied. Angiogenesis is the formation of new blood vessels from existing vessels, and is a key event associated with tumor growth and metastatic dissemination. The inhibition of angiogenesis is thus a promising strategy in cancer treatment. Initial observations in studies conducted in the laboratory on the effects of quinolone derivatives on cancer and endothelial cell lines prompted the researchers to probe selected 2-aryl-3-bromoquinolin-4(1H)-ones and their NMe-4-oxo derivatives for potential antiangiogenic activity. The findings of the investigation showed that test compounds exhibit antiangiogenic activity in a rat aorta assay, with comparable potency to a well-known antiangiogenic agent, 2-methoxyestradiol. These compounds also decreased levels of proangiogenic factors implicated in the pathogenesis of various cancers, such as bFGF and VEGF and PlGF. The most pronounced antiangiogenic activity in all the tests was observed for the 4-fluorinated derivative, and activity decreased when fluorine was replaced with a chlorine atom. The presence of a fluorine atom in a molecule is known to have a profound effect on the biological, chemical and physical properties of such derivatives. The 4_-fluorophenyl NH-4-oxo derivative could thus serve as an excellent lead compound to provide good models for the further design of potent fluorinated 2-arylquinolone derivatives with the potential to serve as antiangiogenic agents for therapeutic application in cancer.
Contact person: Dr PL Mabeta.
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