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.

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.

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies.

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure-activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as "synthetic nucleases", independently of oxygen and pH. Calf thymus-DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for "on demand" biotechnological applications in drug discovery and medicine.

Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies.

Compared to standard treatments for various diseases, photochemotherapy and photo-dynamic therapy are less invasive approaches, in which DNA photocleavers represent promising tools for novel "on demand" chemotherapeutics. A series of p-nitrobenzoyl and p-pyridoyl ester conjugated aldoximes, amidoximes and ethanone oximes were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA. The compounds which possessed appropriate properties were additionally subjected to UVA irradiation at 365 nm. The ability of most of the compounds to photocleave DNA was high at 312 nm, whereas higher concentrations were required at 365 nm as a result of their lower UV absorption. The affinity of selected compounds to calf-thymus (CT) DNA was studied by UV spectroscopy, viscosity experiments and competitive studies with ethidium bromide (EB) revealing that all compounds interacted with CT DNA. The fluorescence emission spectra of the pre-treated EB-DNA exhibited a moderate to significant quenching in the presence of the compounds indicating the binding of the compounds to CT DNA via intercalation as concluded also by DNA-viscosity experiments. For the oxime esters the DNA photocleavage and affinity studies aimed to clarify the role of the oxime nature (aldoxime, ketoxime, amidoxime) and the role of the pyridine and p-nitrophenyl moieties both as oxime substituents and ester conjugates.