Zn(II) complexes of (E)-4-(2-(pyridin-2-ylmethylene)hydrazinyl)quinazoline in combination with non-steroidal anti-inflammatory drug sodium diclofenac: Structure, DNA binding and photo-cleavage studies, antioxidant activity and interaction with albumin

• Published in: Journal of inorganic biochemistry 2020-10, Vol.211, p.111194-111194, Article 111194
• Main Authors: Kakoulidou, Chrisoula, Gritzapis, Panagiotis S., Hatzidimitriou, Antonios G., Fylaktakidou, Konstantina C., Psomas, George
• Format: Article
• Language: English
• Subjects: Free radical scavenging; Interaction with albumin; Interaction with calf-thymus DNA; Plasmid DNA-photocleavage; Quinazoline derivatives; Zn(II) complexes
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2020.111194

The interaction of the novel quinazoline (E)-4-(2-(pyridin-2-ylmethylene)hydrazinyl)quinazoline (L) with Zn2+ was performed in the absence or presence of the non-steroidal anti-inflammatory drug sodium diclofenac (Nadicl) and resulted in the formation of complexes [Zn(L)2](NO3)2·MeOH (1·MeOH) and [Zn(L)(dicl-O)2]·MeOH (2·MeOH), respectively. The two complexes were characterized by IR and 1H NMR spectroscopy and by single-crystal X-ray crystallography. In these complexes, L was tridentately coordinated to Zn(II) via the quinazoline, hydrazone and pyridine nitrogen atoms. Further studies concerning the behavior of the compounds towards calf-thymus (CT) DNA and supercoiled circular pBluescript KS II plasmid DNA (pDNA) have been performed. The complexes may bind to CT DNA via intercalation, with complex 1 showing higher binding affinity than 2. The complexes may cleave pDNA in the absence or presence of irradiation with UVA, UVB or visible light and the most active pDNA-cleavager is compound 1. The binding constants of the compounds for bovine serum albumin were calculated and the subdomain of the albumin where the compounds prefer to bind was determined. The free radical scavenging ability of the compounds was evaluated towards 1,1-diphenyl-picrylhydrazyl and 2,2΄-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals with complex 2 being the most active compound. Thus, complex of type 1 maybe a lead compound for the development of novel DNA-binders and DNA-cleavers or photo-cleavers for medical and biotechnological “on demand” applications, whereas the structure of complex type 2 may provide novel antioxidants and radical scavengers. A novel o-pyridine-hydrazone derivative of 4-quinazoline and its Zn(II) complexes in the absence or presence of diclofenac were characterized and evaluated for their affinity to bovine serum albumin, calf-thymus DNA and plasmid-DNA in the absence or presence of irradiation as well as their ability to scavenge free radicals. [Display omitted] •A novel quinazoline and its two Zn complexes were prepared and characterized.•Intercalation is the most possible binding mode of the complexes to DNA.•The complexes exhibit noteworthy plasmid DNA photocleavage activity.•The compounds may bind tightly and reversibly to bovine serum albumin.•The antioxidant activity of complexes depends on the presence of diclofenac ligand.