PLATINUM(II) AND PLATINUM(IV) SPERMIDINE COMPLEXES - SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL STUDIES

被引:30
作者
NAVARRORANNINGER, C [1 ]
OCHOA, PA [1 ]
PEREZ, JM [1 ]
GONZALEZ, VM [1 ]
MASAGUER, JR [1 ]
ALONSO, C [1 ]
机构
[1] UNIV AUTONOMA MADRID,CTR BIOL MOLEC,E-28049 MADRID,SPAIN
关键词
D O I
10.1016/0162-0134(94)80003-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
By reaction of K2PtCl4 with spermidine we have synthesized two tris-platinum covalent compounds of formula (PtI2)(3)(sper)(2) and (PtCl2)(3)(sper)(2), one ionic compound of formula (sperH(3))(2)(PtCl4)(3), and another one of a covalent nature of formula (PtCl(2)sperH)(2)(PtCl4) having a partially protonated spermidine residue. Treatment of the tris-platinum compounds with hydrogen peroxide and hydrochloric acid led to the production of two compounds of formula cis-transcis-((PtCl2)-Cl-IV(OH)(2))(3)(sper)(2) and cis-((PtCl4)-Cl-IV)(3)(sper)(2), respectively. All of them have been characterized by IR and H-1 MNR spectroscopy and tested for their ability to interact with pUC8 plasmid DNA by the use of UV, CD, and electrophoretic techniques. The results suggest that all of these compounds modify the secondary structure of the double helix. We observed that the alteration in electrophoretic mobility of nicked and closed circular forms of DNA induced by the Pt(II) complexes is higher than that induced by the Pt(IV) complexes. The synthesized compounds were also assayed for antitumor activity in vitro against breast (MDA-MB468) and leukemia (HL-60) tumor cells. Only three of these complexes may be regarded as potential antitumor agents, since their ID50 values are lower than 10 mu g/ml.
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页码:177 / 190
页数:14
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