5-Fluorouracil and 5-fluorouracil-histidine complexes with AlIII, CrIII and FeIII ions and their antitumour activity

Abstract

Complexes of the type [M(L-H)(OH)Cl], [Cr(L-H)(H2O)2(OH)Cl] and [M′(L-H)(L′-H)(H2O)Cl], where L = 5-fluorouracil; L′ = histidine (HISD); M = AlIII or FeIII and M′ = AlIII, CrIII or FeIII were synthesized and characterized. The complexes are insoluble in water and common organic solvents. 5-Fluorouracil is coordinated to the metal ion through the O atom of C(4)=O and the N atom of N(1) while histidine coordinates through the O atom of - COO- and the N atom of - NH2 groups. The μeff values, electronic spectral bands and ESR spectra suggest a polymeric 6-coordinate spin free octahedral stereochemistry for CrIII and FeIII complexes. The in vivo antitumour effect of 5-fluorouracil and its complexes was examined on C3H/He mice against P815 murine mastocytoma. As evident from their T/C values CrIII and FeIII complexes display significant and higher antitumour activity compared to 5-fluorouracil while the AlIII complexes show lower activity. The in vitro results of the complexes on the same cells indicate that CrIII and FeIII complexes show higher inhibition on 3H-thymidine and 3H-uridine incorporation in DNA and RNA replication, respectively. © 1997 Elsevier Science Ltd.