Toxicology and antitumour activity of ferrocenylamines and platinum derivatives

✍ Scribed by R. W. Mason; K. McGrouther; P. R. R. Ranatunge-Bandarage; B. H. Robinson; J. Simpson

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 92 KB
• Volume: 13
• Category: Article
• ISSN: 0268-2605
• DOI: 10.1002/(sici)1099-0739(199903)13:3<163::aid-aoc821>3.0.co;2-k

✦ Synopsis

Toxicity, antitumour, platinum distribution, hepatotoxicity and histology data are presented for a series of ferrocenylamines: [(h-C 5 H 4 (CH 2 ) n NH 2 )FeCp] (n = 0,1) (1,2); [(h-C 5 H 4 CH 2 NHPh)FeCp] (3); [(h-C 5 H 4 CH 2 NMe 2 )FeCp] (4); {[h-C 5 H 4 CH(Me)NMe 2 ]FeCp} (5); [h-C 5 H 4 CH 2 NMe 2 ) 2 Fe] (6); {[1,2h-C 5 H 3 (CHMeNMe 2 )(PPh 2 )] FeCp} (7); {[1,2h-C 5 H 3 (CHMeNMe 2 )(PPh 2 )]-Fe[h-C 5 H 4 PPh 2 ]} (8); and their complexes cis-PtCl 2 L 2 (9); trans -Pt(L)(dmso)X 2 (10); [s -(L)Pt(dmso)X] (11,12) {s-(L)[Pt(dmso)X] 2 } (13); [s-(L)PtP(OPh) 3 Cl] (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 cisplatinresistant sarcoma, but inactive against L-1210 mouse leukaemia and B-16 melanoma. Copyright