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DNA binding and in vitro antileukemic activity of dimeric and tetrameric platinated complexes derived from p ‐isopropylbenzaldehyde thiosemicarbazone
Author(s) -
Quiroga Adoración G.,
Pérez José M.,
Alonso Carlos,
NavarroRanninger Carmen
Publication year - 1998
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(199812)12:12<809::aid-aoc754>3.0.co;2-x
Subject(s) - chemistry , dna , semicarbazone , cisplatin , stereochemistry , in vitro , cytotoxic t cell , platinum , ic50 , cytotoxicity , biochemistry , catalysis , medicine , surgery , chemotherapy
p ‐Isopropylbenzaldehyde thiosemicarbazone ( p ‐is.TSCN) ( 1 ) reacts with [Pt(µ‐Cl)(η 3 ‐C 4 H 7 )] 2 to form a dinuclear [Pt(µ‐Cl)( p ‐is.TSCN)] 2 complex ( 2 ) and a cyclometallated cluster [Pt( p ‐is.TSCN)] 4 ( 3 ). Biological testing of these complexes against HL‐60 and U‐937 human leukemic cells suggest that complexes 2 and 3 may be endowed with important cytotoxic activity properties since they exhibit IC 50 values (50% inhibition of cell growth) in the micromolar range, as does the clinically used drug cisplatin ( cis ‐DDP). Analysis of the interaction of compounds 2 and 3 with DNA indicates that the kinetics of DNA platination due to compounds 2 and 3 is faster than that of cisplatin and that after 24 h of incubation most of the platinum centers are bound to DNA. Thus, it is likely that the cytotoxic activity displayed by compounds 2 and 3 may be correlated with their high level of DNA platination. Copyright © 1998 John Wiley & Sons, Ltd.