Catalytically Generated Ferrocene-Containing Guanidines as Efficient Precursors for New Redox-Active Heterometallic Platinum(II) Complexes with Anticancer Activity

被引:62
作者
Nieto, Daniel [1 ]
Bruna, Sonia [1 ]
Gonzalez-Vadillo, Ana Ma [1 ]
Perles, Josefina [2 ]
Carrillo-Hermosilla, Fernando [3 ]
Antinolo, Antonio [3 ]
Padron, Jose M. [4 ]
Plata, Gabriela B. [4 ]
Cuadrado, Isabel [1 ]
机构
[1] Univ Autonoma Madrid, Fac Ciencias, Dept Quim Inorgan, E-28049 Madrid, Spain
[2] Univ Autonoma Madrid, Serv Interdept Invest SIdI, Lab Difracc Rayos X Monocrystal, E-28049 Madrid, Spain
[3] Univ Castilla La Mancha, Ctr Innovac Quim Avanzada ORFEO CINQA, Dept Quim Inorgan Organ & Bioquim, Fac Ciencias & Tecnol Quim, E-13071 Ciudad Real, Spain
[4] Univ La Laguna, Ctr Invest Biomed Canarias CIBICAN, BioLab, Inst Univ Bioorgan Antonio Gonzalez, San Cristobal la Laguna 38206, Spain
关键词
ARENE RUTHENIUM COMPLEXES; IN-VITRO; MOLECULAR RECOGNITION; ABIOTIC GUANIDINIUM; DNA-BINDING; DERIVATIVES; COORDINATION; AMINOFERROCENE; CHEMISTRY; LIGANDS;
D O I
10.1021/acs.organomet.5b00751
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
The potential of structurally new ferrocene-functionalized guaiiidines as redox-active precursors for the synthesis of heterometallic platinum(II) guanidine complexes with anticancer activity was studied. To this end, an atom-economical catalytic approach was followed by using ZnEt2 to catalyze the addition of aminoferrocene and 4-ferrocenylaniline to N,M-diisopropylcarbodiimide. Furthermore, reaction of a platinum(II) source with the newly obtained guanidines Fc-N=C(NHiPr)(2) (3) and Fc(1,4-C6H4) N=C(NHiPr)(2) (4) provided access to the heterometallic complexes [PtCl2{Fc N-=C(NH1Pr)(2)}(DMSO)] (5), [PtCl2{Fc(1,4-C6H4) N=C(NH1Pr)(2)}(DMSO)] (6), and [PtC12{Fc(1,4-C6H4) N-C=N=((NHPr)-Pr-i)(2)}] (7). Electrochemical studies evidence the remarkable electronic effect played by the direct attachment of the guanidine group to the ferrocene moiety in 3, making its one-electron oxidation extremely easy: Guanidine-based Fe Pt complexes 5 and 6 are active against all human cancer cell lines tested, with GI(50) values in the range 1.4-2.6 mu M and are more cytotoxic than cisplatin in the resistant T-47D and WiDr cell lines.
引用
收藏
页码:5407 / 5417
页数:11
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