Investigation of DNA binding, DNA cleavage, antioxidant, antimicrobial activities and inhibition of topoisomerase i of water soluble ti (IV) phthalocyanine compounds

DNA is an important target for treating genetic diseases most notably cancer. Since cancer cells proliferate rapidly and mortality is high in cancer, it has increased the biological investigation of transition metal complexes as anticancer drugs because of their key impact in clinical therapy. Many anticancer drugs exert their anticancer effects through binding to DNA in various ways, thereby blocking the replication of DNA and inhibiting the growth of cancer cells. The understanding of DNA binding and cleavage is the basis for the design of new, efficient anticancer drugs, their effectiveness depending on the binding mode and affinity towards DNA. The calf thymus (CT) DNA binding of three different water soluble peripherally tetra-substituted titanium (IV) phthalocyanine (Pc) compounds were investigated by using UV-Vis spectroscopy and studies of thermal denaturation in this work. The DNA binding constants (Kb) of Pc compounds were 3.75x104, 2.3x104 and 4.57x104 M-1 respectively. However, DNA cleavage and topoisomerase I inhibition of plasmid pBR322 DNA in the absence and presence of Pc compounds were examined using gel electrophoresis. All Pc compounds cleaved pBR322 DNA via photocleavage pathway and exhibited significant inhibitory effects against topoisomerase I enzyme. In addition, superoxide dismutase (SOD) assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and metal chelating assay were done to examine antioxidant activities of these phthalocyanine compounds. Result of all of these studies that Ti (IV) phthalocyanine compounds can be suitable agent for photodynamic therapy.