Novel Cis- and Trans-Configured Bis(oxime)platinum(II) Complexes: Synthesis, Characterization, and Cytotoxic Activity

Abstract

Novel cis- and trans-configured bis(oxime)platinum(II) complexes have been synthesized and characterized by elemental analyses, IR, electrospray ionization mass spectrometry, multinuclear ((1)H, (13)C, and (195)Pt) NMR spectroscopy, and, in five cases, by X-ray diffraction. Their cytotoxicity was studied in the cisplatin-sensitive CH1 cell line as well as in inherently cisplatin-resistant SW480 cancer cells. Remarkably, every single dihalidobis(oxime)platinum(II) complex (with either a cis or trans configuration) shows a comparable cytotoxic potency in both cell lines, indicating a capacity of overcoming cisplatin resistance. Particularly strong cytotoxicities were observed in the case of trans-[PtCl(2)(R(2)C=NOH)(2)] (R = Me, n-Pr, i-Pr) with IC(50) values in the high nanomolar concentration range in both CH1 and SW480 cancer cells. These complexes are as potent as cisplatin in CH1 cells and up to 20 times more potent than cisplatin in SW480 cells. In comparison to transplatin, the novel compounds are up to 90 (CH1) and 120 times (SW480) more cytotoxic. The previously reported observation that the trans geometry yields a more active complex in the case of [PtCl(2)(Me(2)C=NOH)(2)] could be confirmed for at least two structural analogues.

Synthesis, Characterization, and Cytotoxicity of Platinum(IV) Carbamate Complexes

“…Another possibility is that one of the conformational isomers is significantly less stable than the other two and never accumulates in a high enough concentration to be observed under equilibrium conditions. The use of variable-temperature 195 Pt NMR spectroscopy to distinguish between chemically similar stereoisomers has been reported before 61–64. Our findings here similarly validate this method as a valuable tool for distinguishing isomers that could not otherwise be discerned by the more commonly used 1 H and 13 C NMR spectroscopy.…”

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

“…Some oxime organic derivatives have been reported to have biological effects such as endothelium-independent relaxation in blood-vessels, an increase in the targeting of specific nuclear bases of DNA and oxidative DNA cleavage [42,43]. Oxime-containing Pt(II) compounds have been reported as a novel class of nonclassic platinum-based complexes with interesting antitumor properties, different DNA binding behaviour and a different pattern of protein interaction from those found in classical cisplatin [44,45].…”

Molecular structure, IR spectra, and chemical reactivity of cisplatin and transplatin: DFT studies, basis set effect and solvent effect

“…Due to the different structures of cis-and trans-platinum complexes, they produced different action mechanisms with DNA and in turn led to different biological activities. Several trans-platinum complexes showed better biological activities with efficient anticancer activities and low side effects [7][8][9]. Therefore, illustrating the differences in the geometries of CDDP and TDDP could provide an insight into the interpretation of their different bioactivities and additional information for developing more efficient platinum complexes.…”