Amidoxime platinum(ii) complexes: pH-dependent highly selective generation and cytotoxic activity†
*a
Marina Ya.
Demakova,
a
Vitaliy V.
Suslonov,
c
Alexey A.
Nazarov,
d
Michael A.
Jakupec,
*b
Vadim Yu.
Kukushkin
a
Abstract
The reaction of cis-[PtCl2(Me2![[S with combining low line]](https://www.rsc.org/images/entities/char_0053_0332.gif)
O)2] with 1 equiv. of each of the amidoximes RC(NH2)![[double bond, length as m-dash]](https://www.rsc.org/images/entities/char_e001.gif)
NOH in neutral media in MeOH results in the formation of complexes cis-[PtCl2{RC(NH2)![[N with combining low line]](https://www.rsc.org/images/entities/char_004e_0332.gif)
OH}(Me2O)] (5 examples; 83–98% isolated yields). In the presence of 2 equiv. of NaOH in MeOH solution, the reaction of cis-[PtCl2(Me2O)2] with 1 equiv. of each of the amidoximes RC(NH2)NOH leads to [Pt{RC(H)N![[O with combining low line]](https://www.rsc.org/images/entities/char_004f_0332.gif)
}(Me2O)2] (7 examples; 74–95% isolated yields). All new complexes were characterized by C, H, and N elemental analyses, HRESI+-MS, IR, 1H, 13C{1H}, and CP-MAS TOSS 13C{1H} NMR spectroscopies, and additionally by single-crystal XRD (for seven species). The cytotoxic potency of six compounds was determined in the human cancer cell lines CH1/PA-1, A549, SK-BR-3, and SW480. Generally, the second class of complexes containing chelating amidoximato ligands shows much higher cytotoxicity than the non-chelate amidoxime analogs, despite the lack of easily exchangeable chlorido ligands. Especially, the complex [Pt(p-CF3C6H4C(H)N)(Me2O)2] displays a remarkable activity in the inherently cisplatin resistant SW480 cell line (0.51 μM vs. 3.3 μM).
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