Norfloxacin Zn(II)-based complexes: acid base ionization constant determination, DNA and albumin binding properties and the biological effect against Trypanosoma cruzi

Abstract

Zn(II) complexes with norfloxacin (NOR) in the absence or in the presence of 1,10-phenanthroline (phen) were obtained and characterized. In both complexes, the ligand NOR was coordinated through a keto and a carboxyl oxygen. Tetrahedral and octahedral geometries were proposed for [ZnCl2(NOR)]·H2O (1) and [ZnCl2(NOR)(phen)]·2H2O (2), respectively. Since the biological activity of the chemicals depends on the pH value, pH titrations of the Zn(II) complexes were performed. UV spectroscopic studies of the interaction of the complexes with calf-thymus DNA (CT DNA) have suggested that they can bind to CT DNA with moderate affinity in an intercalative mode. The interactions between the Zn(II) complexes and bovine serum albumin (BSA) were investigated by steady-state and time-resolved fluorescence spectroscopy at pH 7.4. The experimental data showed static quenching of BSA fluorescence, indicating that both complexes bind to BSA. A modified Stern-Volmer plot for the quenching by complex 2 demonstrated preferential binding near one of the two tryptophan residues of BSA. The binding constants obtained (K b ) showed that BSA had a two orders of magnitude higher affinity for complex 2 than for 1. The results also showed that the affinity of both complexes for BSA was much higher than for DNA. This preferential interaction with protein sites could be important to their biological mechanisms of action. The analysis in vitro of the Zn(II) complexes and corresponding ligand were assayed against Trypanosoma cruzi, the causative agent of Chagas disease and the data showed that complex 2 was the most active against bloodstream trypomastigotes.

Norfloxacin La(III)-based complex: synthesis, characterization, and DNA-binding studies

“…In the spectra of La(III) complex, the ν(CO) was affected by interaction with the lanthanum(III) ion and appeared as a shoulder at 1590 cm −1 . Such behavior has been observed in several quinolone metal ion complexes [4,17]. The band at 1628 cm −1 in spectra of the complex was assigned to the asymmetric stretch (ν as ) of the coordinated carboxylate group.…”

“…This band appeared after ionization of the carboxyl group and was characterized by the formation of a resonance structure. This occurrence suggested the involvement of this group in interaction with the metal ion [4,17,18]. 2 shows no bands around 3500 cm −1 for the O-H stretching frequency indicating that O-H has been deprotonated via complex formation, further supporting the interaction of the carboxylate with lanthanum.…”

“…This small shift was expected as there was no hydrogen near the coordination sites. Refat [10,20] and Teixeira [4] assigned a signal at δ = 5.78 ppm to the NOR zwitterionic form and can be observed only when the metal is coordinated to the ketonic and the carboxylic carbons. In our case, we could not observe any signals probably due to low solubility of 2.…”

“…Recently, Luiz et al [2] studied the interaction of norfloxacin with gold(III) and observed that Au 3+ produces pH-dependent spectral modifications, attributed to different interactions with the distinct ionic species. Very recently, Zn(II) complexes with NOR were synthesized and the biological activity of these complexes was directly related to the acid ionization constant (pK) [4]. Spectrophotometric studies showed that the complexes interact with DNA with moderate affinity.…”

Copper(II) Nitroaromatic Schiff Base Complexes: Synthesis, Biological Activity and Their Interaction with DNA and Albumins

“…8 Furthermore, DNA are the most important target for antitumoral drugs, and different types of interactions between small molecules and DNA are possible: these can often cause DNA damage in cancer cells, blocking the division of cancer cells and resulting in cell death. 9 The study of the interaction between small molecules and proteins reveals important information about the binding mechanism, binding constant, mode and site.…”