The effect of histidine on the structure and antitumor activity of metal-5-halouracil complexes

Abstract

The ternary complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) ions with 5-halouracils, viz., 5-fluorouracil (SFU), 5-chlorouracil (5ClU), and 5-bromouracil (5BrU) and the biologically important ligand L-histidine (HISD) have been synthesized and characterized by elemental analysis, conductance measurements, infrared spectra, electronic spectra, and magnetic moment (room temperature) measurements. On the basis of these studies, the structures of the complexes have been proposed. All these ternary complexes were screened for their antitumor activity against Dalton's lymphoma in C 3H/He mice. It was found that only Mn(II)-5BrU-HISD, Co(II)-5BrU-HISD, Cu(II)-SCIU-HISD Cu(II)-5BrU-HISD, Zn(II)-5FU-HISD, and Zn(II)-5BrU-HISD complexes have significant antitumor activity with T/C > 125 % (where T and C represent mean lifespan of treated mice and control mice respectively). The Mn(II)-5FU-HISD, Co(II)-5FU-HISD, Co(II)-5CIU-HISD, Ni(II)-5CIU-HISD, Ni(II)-5BrU-HISD, and Zn(II)-5CIU-HISD complexes are also effective antitumor agents, with T/C > 115 %. The complexes that showed effective antitumor action in vivo were also found to inhibit 3H-thymidine incorporation (DNA replication) in Dalton's lymphoma cells in vitro.