Development of new macrocyclic ligands for Cu(II) complexes
Design of new synthetic metallonucleases
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According to the World Health Organization, cancer is among the second leading death cause globally, and cancer treatment is a challenge in the field of medicinal chemistry. The DNA cleavage activity of a metallonuclease is related to its capability to generate toxic reactive oxygen species (ROS) in a reductive environment. In this scenario, 1,4,7,10-tetraazacyclododecane is a fully exploited ligand, thanks to the good stability constants towards many metal centres. Exploiting Cu(II) as metal core, the heteroatom substitution together with a coupling of this macrocyclic ligand with the DNA tar...
According to the World Health Organization, cancer is among the second leading death cause globally, and cancer treatment is a challenge in the field of medicinal chemistry. The DNA cleavage activity of a metallonuclease is related to its capability to generate toxic reactive oxygen species (ROS) in a reductive environment. In this scenario, 1,4,7,10-tetraazacyclododecane is a fully exploited ligand, thanks to the good stability constants towards many metal centres. Exploiting Cu(II) as metal core, the heteroatom substitution together with a coupling of this macrocyclic ligand with the DNA targeting function anthraquinone were already performed, in order to improve the efficacy. The aim of the present book was to synthesise new ligands for Cu(II) metallonucleases, where the ligand itself could be redox active, in order to enhance the ROS concentration and consequently the catalytic activity of the nuclease. Moreover, the ligands under study were functionalised by an anthraquinonemoiety, and these compounds were tested towards DNA intercalation, alone and after incubation with Cu(II) salt.
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