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

• Published in: European journal of inorganic chemistry 2020-03, Vol.2020 (11-12), p.1027-1039
• Main Authors: Marchetti, Fabio, Nicola, Corrado, Pettinari, Riccardo, Pettinari, Claudio, Aiello, Iolinda, Deda, Massimo, Candreva, Angela, Morelli, Sabrina, Bartolo, Loredana, Crispini, Alessandra
• Format: Article
• Language: English
• Subjects: Acylpyrazolones; Antiproliferation; Antiproliferatives; Apoptosis; Breast cancer; Chemical analysis; Crystal structure; Enantiomers; Ethanol; Inorganic chemistry; Mass spectrometry; NMR; Nuclear magnetic resonance; Oxygen atoms; Pyrazolones; Recrystallization; Single crystals; Structure elucidation; Toxicity; Zinc; Zinc compounds
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201900775

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. Zinc(II) acylpyrazolone complexes were synthesized, decorated with a long aliphatic chain or a cyclohexyl group in the acyl moiety of the ligands, the latter displaying antiproliferative activity against MCF‐7 human breast cancer cell line, additionally improved when an ancillary bipyridine is present in the zinc coordination environment.