RESUMEN
In this study, several unsymmetrical Schiff bases and their cobalt and manganese complexes have been synthesized and characterized. The unsymmetrical Schiff bases were prepared from reaction of o-phenylendiamine derivatives with 1-hydroxy-2-acetonaphthone and then the product was reacted with the following aldehydes: salicyaldehyde, 2-hydroxynaphthaldehyde, 2-pyridinecarboxaldehyde and 2-qinolinecarboxaldehyde to produce the desired tetradentate unsymmetrical Schiff base ligands H2SL, H2NL, HPYL and HQN, respectively. Reaction of these ligands with cobalt and manganese salts produced complexes of the general formula [M(SL)], [(NL)], [M(PYL)] and [M(QL)]. All the complexes were characterized by elemental analysis, infrared spectroscopy, UV-visible spectroscopy, electrical conductivity and magnetic susceptibility measurements. The prepared complexes were examined for their anti-bacterial activity using gram-positive and gram-negative pathogens. The following complexes showed strong antibacterial activity against Staphylococcus aureus: MnSL1, MnSL2 and MnSL3. The genotoxic activity of four complexes, which are MnNL1, MnSL1, CoNL1 and CoSL1, were examined using 8-hydroxy-2-deoxy guanosine (8-OHdG) assay in cultured human blood lymphocytes. All examined complexes were found to be genotoxic at examined concentrations (0.1-100 µg/mL), but with variable magnitudes (p < 0.05). The levels of 8-OHdG induced by MnNL1 and MnSL1 were significantly higher than that induced by CoNL1 and CoSL1 ones. In general, the order of mutagenicity of the compounds is MnSL1 > MnNL1 > CoSL1 > CoNL1. In conclusion, some of the prepared complexes showed some biological activities that might be of interest for future research.
Asunto(s)
Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Bases de Schiff/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Cobalto/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Relación Dosis-Respuesta a Droga , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Manganeso/química , Pruebas de Mutagenicidad , Fenilendiaminas/química , Bases de Schiff/síntesis química , Bases de Schiff/químicaRESUMEN
The utilization of Schiff bases in the industrial and pharmaceutical fields has led to an increase in their syntheses and evaluation of their biological activities. In this study, we described the synthesis and genotoxicity of two Schiff bases that share common platform in their construction, namely, naphthalene, and are complexed to either Cu(II) or Zn(II). The genotoxicity of these complexes was evaluated in cultured lymphocytes using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs), and in rats using the urine 8-OH-2-deoxyguanosine (8-OH-dG) assay. The results showed that the examined complexes are genotoxic, but with different degrees. The order of genotoxicity of the complexes at 10 µg/mL was: Cu(L3)(NCS)(H2O) > Zn(L3)(NCS)(H2O) > Cu(L2)(NCS) > Zn(L2)(NCS), where L2 and L3 are the conjugate bases of N-(8-quinolyl)napthaldimine and N-(anilinyl)napthaldimine, respectively. However, at the 1-µg/mL concentration, only the Cu(L3)(NCS)(H2O) complex induced significant CAs, whereas at the 0.1-µg/mL concentration, only Cu(L3)(NCS)(H2O) and Zn(L2)(NCS) complexes induced significant SCEs, compared to controls. In the urine 8-OH-dG assay, all complexes at 10 mg/100 g body weight (b.w.) were found to cause DNA damage with the following order: Cu(L3)(NCS)(H2O) > Zn(L2)(NCS) > Zn(L3)(NCS)(H2O) > Cu(L2)(NCS), whereas no significant DNA damage was observed in animals exposed to 1 and 0.1 mg/100 g b.w. (p > 0.05). In conclusion, the two examined Schiff base complexes are found to induce DNA damage, but with different degrees.
Asunto(s)
Cobre/metabolismo , Daño del ADN/efectos de los fármacos , Pruebas de Mutagenicidad/métodos , Naftalenos/química , Bases de Schiff/toxicidad , Zinc/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Aberraciones Cromosómicas/inducido químicamente , Cobre/toxicidad , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Relación Dosis-Respuesta a Droga , Linfocitos/efectos de los fármacos , Estructura Molecular , Ratas , Bases de Schiff/química , Bases de Schiff/metabolismo , Intercambio de Cromátides Hermanas/efectos de los fármacos , Espectrofotometría Ultravioleta , Zinc/toxicidadRESUMEN
The in vivo interactions of structurally-related Ni(II) and Fe(III) Schiff base complexes based on N-(8-quinolyl)salicylaldimine (HL(1)) and N-(8-quinolyl)napthaldimine (HL(2)) ligands with DNA molecules in the bone-marrow cells of rats were demonstrated using chromosomal aberrations (CAs) assay. The complexes differ by one aromatic group on the aldehyde site of the Schiff base (basicity or lipophilicity), or by the type of the central metal ions (Ni(II) or Fe(III)). Animals were injected intraperitoneally (i.p) with different concentrations of each drug, and CAs were examined in bone-marrow cells, 15 hours later. A significant increase in the frequency of CAs was induced upon treatment with 15 mg / kg weight of L(1) complexes (P < 0.001), and not with L(2) complexes (P > 0.05). Also, the magnitude of aberrations induced by L(1)-Ni(II) was higher than that induced by L(1)-Fe(III) (P < 0.01). The binding data, estimated using UV-Visible absorption technique, showed that the metal binding of HL(1) was much greater than that of HL(2) and that the affinity of HL(1) towards Ni(II) is higher than that for Fe(III) ions. Thus, the trends in the presented in vivo results signify the important role of complex stability in predicting the clastogenicity of metal-ion-chelating Schiff base drugs.