Zinc(II) Complexes of Acylpyrazolones Decorated with a Cyclohexyl Group Display Antiproliferative Activity Against Human Breast Cancer Cells

Abstract

Five‐ and six‐coordinated zinc(II) complexes, [Zn(QR)2(H2O)] (1–2) and [Zn(QR)2(L)] (3–8) {HQR = 4‐R(C=O)‐5‐pyrazolones in general, in detail HQC17, R = –(CH2)16CH3, HQCy, R = –C6H11; L = bipy, tmeda or en} have been synthesized and characterized by IR, 1H and 13C NMR, UV/Visible spectroscopy, elemental analysis, TGA and ESI mass spectrometry. The square pyramidal complex [Zn(QC17)2(H2O)] (1) has been structurally characterized, together with a trans octahedral [Zn(QCy)2(EtOH)2] (2b) species obtained by recrystallization of [Zn(QCy)2(H2O)] (2) from ethanol. Additionally, in both complexes [Zn(QCy)2(bipy)] (4) and [Zn(QC17)2(tmeda)] (5) structurally characterized by single crystal X ray diffraction, the same amount of Δ and Λ enantiomers are present, with the only difference related to the mutual disposition of the different type of the QR coordinated oxygen atoms. The cytotoxicity of the complexes [Zn(QCy)2(H2O)] (2), [Zn(QCy)2(bipy)] (4) and [Zn(QCy)2(en)] (8) has been evaluated in vitro against MCF‐7 human breast cancer cell line in a biohybrid membrane system. Results revealed that zinc complexes possess antiproliferative activity inducing apoptosis by activation of caspase‐3 and p‐JNK.