5-Fluorouracil and 5-fluorouracil-histidine complexes with Al III, Cr III and Fe III ions and their antitumour activity

Abstract

Complexes of the type [M(L-H)(OH)Cl], [Cr(L-H)(H 2O) 2(OH)Cl] and [M′(L-H)(L′-H)(H 2O)Cl], where L = 5-fluorouracil; L′ = histidine (HISD); M = Al III or Fe III and M′ = Al III, Cr III or Fe III 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 −NH 2 groups. The μ eff values, electronic spectral bands and ESR spectra suggest a polymeric 6-coordinate spin free octahedral stereochemistry for Cr III and Fe III complexes. The in vivo antitumour effect of 5-fluorouracil and its complexes was examined on C 3H/He mice against P815 murine mastocytoma. As evident from their T/C values Cr III and Fe III complexes display significant and higher antitumour activity compared to 5-fluorouracil while the Al III complexes show lower activity. The in vitro results of the complexes on the same cells indicate that Cr III and Fe III complexes show higher inhibition on 3H-thymidine and 3H-uridine incorporation in DNA and RNA replication, respectively.