In vivo cytogenetic studies on rat’s bone-marrow cells of structurally related Schiff base complexes

Abstract

The in vivo interactions of structurally-related Ni(II) and Fe(III) Schiff base complexes based on N-(8-quinolyl)salicylaldimine (HL¹) and N-(8-quinolyl)napthaldimine (HL²) 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 L¹ complexes (P < 0.001), and not with L² complexes (P > 0.05). Also, the magnitude of aberrations induced by L¹-Ni(II) was higher than that induced by L¹-Fe(III) (P < 0.01). The binding data, estimated using UV-Visible absorption technique, showed that the metal binding of HL¹ was much greater than that of HL² and that the affinity of HL¹ 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.

Keywords::

• N-(8-quinolyl)salicylaldimine
• N-(8-quinolyl)napthaldimine
• chromosome aberrations
• structure-activity relationship
• in vivo cytogenetic study
• complex drug stability
• bone-marrow cells

Acknowledgments

The authors wish to thank JUST for their support.

Declaration of interest

The authors wish to thank Yarmouk University (Irbid, Jordan) for their financial support (grant no. 2008/4). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.