Toxicology and antitumour activity of ferrocenylamines and platinum derivatives

Abstract

Toxicity, antitumour, platinum distribution, hepatotoxicity and histology data are presented for a series of ferrocenylamines: [(η‐C5H4(CH2)nNH2)FeCp] (n = 0,1) (1,2); [(η‐C5H4CH2NHPh)FeCp] (3); [(η‐C5H4CH2NMe2)FeCp] (4); {[η‐C5H4CH(Me)NMe2]FeCp} (5); [η‐C5H4CH2NMe2)2Fe] (6); {[1,2η‐C5H3(CHMeNMe2)(PPh2)]FeCp} (7); {[1,2η‐C5H3(CHMeNMe2)(PPh2)]Fe[η‐C5H4PPh2]} (8); and their complexes cis‐PtCl2L2 (9); trans ‐ Pt(L)(dmso)X2 (10); [σ ‐ (L)Pt(dmso)X] (11,12) {σ‐(L)[Pt(dmso)X]2} (13); [σ‐(L)PtP(OPh)3Cl] (14) (L = ferrocenylamine). The toxicity order is 1–3 ≫ 4–8 for the ferrocenylamines; the lower toxicity of tertiary amines may be due to protonation in vivo. Pt(II) complexes all show increased toxicity over the ligand. Liver, not kidney, damage is the norm from i.p. injection of 1–14 and detailed platinum distribution, blood serum and histology studies with 9 and 11 show that the platinum distribution does not correlate with liver dysfunction. Complexes 9–14, but not 1–8, were active against P‐388 mouse leukaemia tumour and cisplatin‐resistant sarcoma, but inactive against L‐1210 mouse leukaemia and B‐16 melanoma. Copyright © 1999 John Wiley & Sons, Ltd.

Synthesis, characterization and antitumor activity of 1,2-disubstituted ferrocenes and cyclodextrin inclusion complexes

“…Neither ferrocene nor the monosubstituted derivative 1 exhibited activity. These two compounds were also found to be inactive against P-388 mouse leukaemia tumor [61]. On the other hand, Fiorina et al reported that some ferrocenyl polyamine compounds were active against P-388 lymphocytic leukaemia in mice [62].…”

Water-soluble platinum(II) complexes of diamine chelating ligands bearing amino-acid type substituents: the effect of the linked amino acid and the diamine chelate ring size on antitumor activity, and interactions with 5′-GMP and DNA

“…DNA intercalators, amino acids and their derivatives are good examples of such bioactive groups. Since 1975 different Pt(II) complexes bearing amino acids or peptides have been described [19][20][21][22][23], attracting the attention of scientists until now [24][25][26][27][28][29].…”

1-Methyl-4-ferrocenylmethyl-3,5-diphenylpyrazole: A versatile ligand for palladium(II) and platinum(II)

“…The results obtained have shown that compound 3 is more prone to bind to these ions than the non-methylated derivative Since platinum(II) compounds containing pyrazole ligands have greater antitumoral activity and lower toxicity than cis-[PtCl 2 (NH 3 ) 2 ] [6c,7h] and some platinum(II) complexes derived from N-donor ferrocenyl ligands also exhibit antitumoral activity [46], the new platinum(II) derivatives presented in this work containing simultaneously a ferrocenyl-and a pyrazolyl units appear to be specially attractive for further studies as antitumoral drugs.…”