Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands

Abstract

Bis(pyrazol-1-yl)acetic acid (HC(pz)2COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pzMe2)2COOH) were converted into the methyl ester derivatives 1 (LOMe) and 2 (L2OMe), respectively, and were used for the preparation of Cu(I) and Cu(II) complexes 3–10. The copper(II) complexes were prepared by the reaction of CuCl2·2H2O or CuBr2 with ligands 1 and 2 in methanol solution. The copper(I) complexes were prepared by the reaction of Cu[(CH3CN)4]PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine with LOMe and L2OMe in acetonitrile solution. Synchrotron radiation-based complementary techniques (XPS, NEXAFS, and XAS) were used to investigate the electronic and molecular structures of the complexes and the local structure around copper ions in selected Cu(I) and Cu(II) coordination compounds. All Cu(I) and Cu(II) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human cancer cell lines, and were able to overcome cisplatin resistance. Noticeably, Cu complexes appeared much more effective than cisplatin in 3D spheroid cultures. Mechanistic studies revealed that the antitumor potential did not correlate with cellular accumulation but was consistent with intracellular targeting of PDI, ER stress, and paraptotic cell death induction.

Mixed ligand copper(ii)-diimine complexes of 2-formylpyridine-N4-phenylthiosemicarbazone: diimine co-ligands tune thein vitronanomolar cytotoxicity

“…The stability of complexes in buffer and cell culture medium was monitored using 0.5% DMSO-PBS pH 7.4 buffer and 0.5% DMSO-RPMI (without phenol red) cell culture medium using the electronic absorption spectral technique. 67 The absorption spectra were recorded at different time intervals of 0, 24, 36, 48 h at 37 °C, and the results reveal that all the complexes are stable in buffer medium up to 48 h (Fig. S4 †).…”

Novel Biotinylated Cu(II)-Phenanthroline Complexes: 2D and 3D Cytotoxic Activity and Mechanistic Insight

“…Altogether, these data confirm that DNA is a major target for this class of complexes and the interaction is mainly by intercalation. On the other hand, some reports highlighted protein disulphide isomerase (PDI) as an emerging target for copper complexes [ 27 ]. On this basis, we also evaluated the ability of our complexes to act as PDI inhibitors.…”

“…MDA-MB-231 cells (2.5 × 10 6 ) were seeded in 75 cm 2 flasks in a growth medium (20 mL). Following 24 h, cells were treated for 24 h with tested complexes and samples processed as previously described [ 27 ].…”

Azo naringenin‐based copper (II) complex as DNA binder: Synthesis, spectroscopic characterization, and diverse biological potentials

“…Temp (Δν = ν asym À ν sym ), which equals 148 cm À1 and is lower than that of NaOAc (Δν = 164 cm À1 ). 35,36 Depending on the results discussed so far, the structural formula of the current copper complex can be depicted as shown in Figure 4.…”