Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring—the dichloro[(±)-trans-N,N′-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC₅₀ 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC₅₀ 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC₅₀ values in the lower micromolar region.

Reactive oxygen species (ROS) play a key role in the regulation of adipogenesis. The aim of our study was to investigate the effect of quercetin (QCT) supplement on obese adipose tissue metabolism of 30-week-old diabetic Zucker rats (ZDF), not well examined yet. QCT was administered orally at dose of 20 mg/kg body weight/day for 6 weeks. Adipocytes from subcutaneous adipose tissue (ScWAT) were isolated and their size was evaluated by light microscopy. Gene expression of adipogenic markers in subcutaneous and visceral adipose tissue was determined by real-time PCR and expression of proteins involved in lipid and glucose metabolism was determined in ScWAT by immunoblotting. Obese ZDF rats suffered from diabetes, hyperinsulinemia and had higher index HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). Treatment with QCT had no significant impact on these metabolic disorders in genetic model of obesity and type 2 diabetes used in our study. Nevertheless, QCT reduced expression of inflammatory cytokine tumour necrosis factor alpha in ScWAT and also visceral adipose tissue and up-regulated expression of anti-inflammatory adiponectin in ScWAT. A shift in redox equilibrium was detected via inhibition of pro-oxidant genes by QCT. Furthermore, QCT reduced adipocyte size in ScWAT, down-regulated expression of fatty acid synthase and adipogenic markers, and moreover stimulated expression of proteolytic enzymes. These changes likely resulted in reduced fat deposition in ScWAT, which was reflected in the elevated circulated levels of free fatty acids in QCT-treated obese ZDF rats compared with obese untreated controls. This increase could, at least in part, explain why we did not observe an improvement in systemic metabolic health by QCT in our model. In conclusion, our study suggests that preventive treatment with QCT might be more effective than its administration in the stage of fully developed diabetes, and further research in this area is needed.

Two copper(II) complexes (Cu-L1, Cu-L2) derived from 2,3-substituted quinazolinone Schiff base ligands (L1, L2) were prepared to examine their anticancer activity. Compounds were characterized using various spectroscopic methods (FTIR, NMR, UV-vis) and quantum-chemical calculations. The biological effects of Cu(II) complexes bearing quinazolinone scaffolds were evaluated on two cancers’ cell lines (breast—MCF-7 and lung—A549), as well as on untransformed cells (keratinocytes—HaCaT). Copper complexes were highly cytotoxic, with IC₅₀ in the low micromolar range, while the quinazoline ligands L1 and L2 remained inactive in inhibiting cell proliferation. Antioxidant activity was investigated in the model systems using DPPH and FRAP assays. The Cu-L1 and Cu-L2 complexes exhibited enhanced DPPH free radical scavenging efficiency compared to the L1 and L2 ligands, but their reducing ability was comparable to that of the free ligands. Evaluation of oxidative stress in vitro carried out by staining cells with various ROS-specific indicators showed reduced production of superoxide anion radical and hydrogen peroxide after treatment of cells with copper complexes. Such a negative impact on ROS formation in cells can lead to cellular redox imbalance and consequent cell death, among others, by inducing apoptosis and/or necrosis, depending on the copper complex used. We hypothesize that the high cytotoxic activity of the investigated copper complexes is apparently the result of multiple mechanisms of action, and the imbalance in the cellular antioxidant system partly contributes to the overall cytotoxic effect.

Background: Chronic inflammatory diseases are associated with qualitative and quantitative changes in lipid and lipoprotein metabolism, including high density lipoproteins (HDLs), increasing patients´ susceptibility to atherosclerosis and cardiovascular mortality. Given the liver’s central role in lipoprotein metabolism and systemic inflammation, we aimed to develop and investigate an in vitro model of inflammation-induced hepatic metabolic changes. Methods and Results: To better approximate in vivo conditions, where systemic inflammation exposes the liver to a complex environment rich in cytokines and inflammatory mediators, we exposed human hepatocarcinoma HepG2 cells to conditioned media (CM) from THP-1-derived macrophages using phorbol-12-myristate-13-acetate (PMA) and lipopolysaccharide (LPS). The effect of CM on mRNA expression in HepG2 was tested by quantitative real-time PCR or protein expression by Western blot analysis. Even short-term exposure to CM (2–4 h) led to a significant change in the mRNA expression of inflammatory genes and several transcription factors (e.g., TNF-α, NF-κB, PPARα, and LRH-1). This change was accompanied by alternations in the expression of lipoprotein-associated genes at different time points (e.g. SAA, LDLr, ApoA1, ABCA1, PON1, and PCSK9). After 24 h of exposure, no effect on HepG2 viability was observed. Conclusion: In our model, we observed several significant inflammation-induced changes in hepatic lipoprotein metabolism, making it a valuable in vitro system for further mechanistic studies.