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Toxicology and antitumour activity of ferrocenylamines and platinum derivatives
Author(s) -
Mason R. W.,
McGrouther K.,
RanatungeBandarage P. R. R.,
Robinson B. H.,
Simpson J.
Publication year - 1999
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/(sici)1099-0739(199903)13:3<163::aid-aoc821>3.0.co;2-k
Subject(s) - chemistry , cisplatin , toxicity , platinum , stereochemistry , ligand (biochemistry) , in vivo , medicinal chemistry , biochemistry , chemotherapy , medicine , receptor , biology , organic chemistry , microbiology and biotechnology , catalysis
Toxicity, antitumour, platinum distribution, hepatotoxicity and histology data are presented for a series of ferrocenylamines: [(η‐C 5 H 4 (CH 2 ) n NH 2 )FeCp] ( n = 0,1) ( 1 , 2 ); [(η‐C 5 H 4 CH 2 NHPh)FeCp] ( 3 ); [(η‐C 5 H 4 CH 2 NMe 2 )FeCp] ( 4 ); {[η‐C 5 H 4 CH(Me)NMe 2 ]FeCp} ( 5 ); [η‐C 5 H 4 CH 2 NMe 2 ) 2 Fe] ( 6 ); {[1,2η‐C 5 H 3 (CHMeNMe 2 )(PPh 2 )]FeCp} ( 7 ); {[1,2η‐C 5 H 3 (CHMeNMe 2 )(PPh 2 )]Fe[η‐C 5 H 4 PPh 2 ]} ( 8 ); and their complexes cis ‐PtCl 2 L 2 ( 9 ); trans ‐ Pt(L)(dmso)X 2 ( 10 ); [σ ‐ (L)Pt(dmso)X] ( 11 , 12 ) {σ‐(L)[Pt(dmso)X] 2 } ( 13 ); [σ‐(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 cisplatin‐resistant sarcoma, but inactive against L‐1210 mouse leukaemia and B‐16 melanoma. Copyright © 1999 John Wiley & Sons, Ltd.