No abstract

Popular treatments of cancer such as Cisplatin have many drawbacks, including the development of chemoresistance in cancer cells and serious side effects such as nephrotoxicity and neurotoxicity. Therefore, there is a need for development of more efficient, target‐specific, and less toxic cancer drugs. Copper complexes have shown to be a promising alternative, partly because copper, an essential element for most aerobic organisms, is involved in many biological pathways as structural and catalytic cofactor. Additionally, studies have shown a correlation between serum copper level and different aspects of cancers. We have synthesized and evaluated the biological activities of Cu‐quinoline thiazole (CuQ(oBt)) and Cu‐pyridine thiazole (Cu(Py(oBt))2). The nuclease activities of these complexes were visualized via gel electrophoresis. We found that Cu(Py(oBt))2 and CuQ(oBt), in the presence of a reductant, convert supercoil (SC) DNA to the single‐nicked (SN) and double‐nicked (DN) forms with high but different efficiencies. The binding of complexes to DNA was further investigated using electronic absorption and fluorescence spectroscopy. Fluorescence spectroscopy with bovin serum albumin (BSA) showed that the complexes can bind to serum proteins. The comparison of results provides insights for aspects of the ligand frames that affect the DNA‐binding, protein‐binding, and nuclease activities for copper complexes.

Transition metal based complexes that exhibit nuclease activity have garnered interest due to their chemotherapeutic applications. Cisplatin has been regarded as one of the most effective drugs, however toxicities and drug resistance has limited its clinical use. Copper (II) centered complexes are promising due to the importance of copper for a range of physiological processes, including enzyme and protein activity. Copper is also found in high concentrations in tumor cells as it is needed for angiogenesis. We have synthesized and characterized several copper complexes that are derived from a thiazole ligand backbone that express nuclease activity: [Cu(8OHQ(oBt))Cl2] and [Cu(8OQ)(oBt))Cl(MeOH)]. These complexes contain step‐wise structural modifications allowing structure function comparisons to be made. DNA cleavage and binding studies were carried out using gel electrophoresis, ethidium bromide, and UV‐Vis Spectroscopy. Quantitative analyses from each of the above studies were used to assess nuclease efficiency, binding efficiency and the copper compounds’ interaction with DNA and BSA.