RCMI Pilot Project- Zuzana Baran

Project title: : Novel Schiff-base ligands and transition metal complexes as metallodrugs for cancer treatment

PI: Zuzana Baran

Email: zbaran@xula.edu

Project Summary/Abstract :

Management and treatment of cancer diagnoses, specifically breast, lung, and prostate cancers pose significant challenges of health related to affordable and more readily available treatment options with less detrimental side-effects. Current understanding of the mechanism on a molecular level for treatment with metallodrugs involves the apoptotic pathway upon covalent binding of the metallodrugs to DNA. Biologically active metal centers, such as copper, found in various metalo-enzymes coordinate usually by methionine, glutamate, cysteine or histidine moieties. Copper has interesting redox properties usable in radical scavenging and reduction of oxidative stress.

The ability of copper to bind to a wide range of ligands forming stable complexes enables modulation of the hard/soft character of copper and its redox properties. Copper (II) complexes of Schiff bases in particular exhibit promising anticancer activities with DNA intercalative or oxidative DNA cleaving mechanism of action or are being considered nuclease mimetic. These biological activities will be employed in the development of novel synthetically viable and shelf-stable Schiff-base ligands through the inclusion of naturally occurring amino acids surrounding the copper center. Further, the corresponding copper complexes will be studied for their biological activity, including cytotoxicity, DNA intercalative or oxidative cleaving mechanism.