Copper(ii) complexes with NNO ligands: synthesis, crystal structures, DNA cleavage, and anticancer activities. Issue 48 (3rd December 2019) - Yang, Ping
Abstract : The copper(ii ) complexes of aroylhydrazone ligands exhibit strong DNA binding affinity and prominent ds DNA cleavage and cytotoxicity. Abstract : Three novel copper(ii ) complexes, Cu(L1 )2 (1 ), Cu(L2 )2 ·2DMF (2 ), and Cu(L3 )2 ·2DMF (3 ), were synthesized using three aroylhydrazone ligands, ( E )-2-hydroxy- N ′-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL1 ), ( E )-3-hydroxy- N ′-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL2 ) and ( E )-4-hydroxy- N ′-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL3 ). The complexes were characterized by elemental analysis, infrared (IR), and Ultraviolet-visible light (UV-vis) spectroscopy. The X-ray crystal structures of the complexes all possess a distorted octahedral coordination geometry. Both an absorption spectral titration and a competitive binding assay (ethidium bromide, 4′, 6-diamidino-2-phenylindole (DAPI), and methyl green) revealed that complexes 2 and 3 bind readily to calf thymus DNA (ctDNA) through intercalative and minor groove binding modes. Complexes 2 and 3 also exhibited oxidative cleavage of supercoiled plasmid DNA (pUC19) in the presence of ascorbic acid as an activator. Cytotoxicity studies showed that complexes 2 and 3 possessed high cytotoxicities toward the HeLa human cervical cancer cell line, but weak toxicities toward the L929 normal mouse fibroblast cell line. We therefore have reason to believe that complexes 2 and 3 both show potential as promising anticancer candidate drugs.