Structural investigation of interactions between halogenated flavonoids and the lipid membrane along with their role as cytotoxic agents.

This study focuses on understanding the structural and molecular changes in lipid membranes under the influence of six halogenated flavonoid derivatives differing in the number and position of substitution of chlorine and bromine atoms (D1-D6). Utilizing various analytical techniques, including fluorometric methods, dynamic light scattering (DLS), attenuated Fourier transform infrared spectroscopy (ATR- FTIR), and FT-Raman spectroscopy, the research aims to elucidate the mechanisms underlying the interaction of flavonoids with cell membranes. Additionally, the study includes in silico analyses to explore the physicochemical properties of these compounds and their potential pharmaceutical applications, along with toxicity studies to assess their effects on cancer, normal, and red blood cells. Our study showed the ability of halogenated derivatives to interact mostly with the outer part of the membrane, especially in the lipid heads region however, some of them were able to penetrate deeper into the membrane and affect the fluidity of hydrocarbon chains. The potential to reduce cancer cell viability, the lack of toxicity towards erythrocytes, and the favourable physicochemical and pharmacokinetic properties suggest these halogenated flavonoids potential candidates for exploring their potential for medical use.

Malvidin and Its Mono- and Di-Glucosides Forms: A Study of Combining Both In Vitro and Molecular Docking Studies Focused on Cholinesterase, Butyrylcholinesterase, COX-1 and COX-2 Activities.

Malvidin, one of the six most prominent anthocyanins found in various fruits and vegetables, may possess a wide range of health-promoting properties. The biological activity of malvidin and its glycosides is not entirely clear and has been relatively less frequently studied compared to other anthocyanins. Therefore, this study aimed to determine the relationship between the structural derivatives of malvidin and their anti-cholinergic and anti-inflammatory activity. The study selected malvidin (Mv) and its two sugar derivatives: malvidin 3-O-glucoside (Mv 3-glc) and malvidin 3,5-O-diglucoside (Mv 3,5-diglc). The anti-inflammatory activity was assessed by inhibiting the enzymes, specifically COX-1 and COX-2. Additionally, the inhibitory effects on cholinesterase activity, particularly acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), were evaluated. Molecular modeling was also employed to examine and visualize the interactions between enzymes and anthocyanins. The results revealed that the highest inhibitory capacity at concentration 100 µM was demonstrated by Mv 3-glc in relation to AChE (26.3 ± 3.1%) and BChE (22.1 ± 3.0%), highlighting the crucial role of the glycoside substituent at the C3 position of the C ring in determining the inhibitory efficiency of these enzymes. In addition, the glycosylation of malvidin significantly reduced the anti-inflammatory activity of these derivatives compared to the aglycone form. The IC50 parameter demonstrates the following relationship for the COX-1 enzyme: Mv (12.45 ± 0.70 µM) < Mv 3-glc (74.78 ± 0.06 µM) < Mv 3,5-diglc (90.36 ± 1.92 µM). Similarly, for the COX-2 enzyme, we have: Mv (2.76 ± 0.16 µM) < Mv 3-glc (39.92 ± 3.02 µM) < Mv 3.5-diglc (66.45 ± 1.93 µM). All tested forms of malvidin exhibited higher activity towards COX-2 compared to COX-1, indicating their selectivity as inhibitors of COX-2. Theoretical calculations were capable of qualitatively replicating most of the noted patterns in the experimental data, explaining the impact of deprotonation and glycosylation on inhibitory activity. It can be suggested that anthocyanins, such as malvidins, could be valuable in the development of treatments for inflammatory conditions and Alzheimer's disease and deserve further study.

An analysis of interactions between three structurally diverse anthocyanidins, as well as their glucosides, and model biological membranes, albumin, and plasmid DNA.

The aim of the study is to investigate the differences in the interaction of three structurally diverse anthocyanidins, namely peonidin, petunidin, and delphinidin, as well as their glucosides with model biological membranes, human albumin, and plasmid DNA in order to look into their structure-activity relationships. Fluorimetric studies, as well as ATR-FTIR analyses, were jointly used in order to determine the changes observed in both the hydrophilic and hydrophobic layers of cell-mimic membranes (MM) which reflected the membrane lipid composition of tumour cells and red blood cell membranes (RBCM). Our results showed that anthocyanins and anthocyanidins can cause an increase in the packing order of the polar heads of lipids, as well as interact with their deeper layers by reducing the fluidity of lipid chains. The results presented here indicate that all compounds tested here possessed the ability to bind to human serum albumin (HSA) and the presence of a glucose molecule within the structures formed by anthocyanidin reduces their ability to bind to proteins. Using fluorescence correlation spectroscopy, it was demonstrated that the compounds tested here were capable of forming stable complexes with plasmid DNA and, particularly, strong DNA conformational changes were observed in the presence of petunidin and corresponding glucoside, as well as delphinidin. The results we obtained can be useful in comprehending the anthocyanins therapeutic action as molecular antioxidants and provide a valuable insight into their mechanism of action.

Analytical and Theoretical Studies of Antioxidant Properties of Chosen Anthocyanins; A Structure-Dependent Relationships.

The relationship between the structure and the antiradical and antioxidant activities of three anthocyanidins, namely peonidin, petunidin, and delphinidin, and their glucosides was investigated in this study. The ability of anthocyanins to scavenge free radicals was determined using DPPH● assay, whereas the inhibition of peroxidation in liposomes in relation to a model membrane that imitated the composition of a lipid membrane in tumor cells was specified using the fluorimetric method. To explore this issue at the atomistic level, density functional theory studies were applied. It was shown that glycosides performed better than anthocyanidins in protecting membranes against oxidation. The highest redox potential was demonstrated by anthocyanidins with the highest number of hydroxyl groups in the B ring in the order as follows: (Dp > Pt > Pn), and the same relationship was proven for their glucosides. The majority of the compounds studied here proved to be better antioxidants than ascorbic acid. They showed consistent electrodonating properties and though the f-HAT mechanism became more feasible with each consecutive deprotonation. Glycosylation did not have a direct impact on reactivity, apart from peonidin and petunidin in the study of which it was found that this process was responsible for lifting off steric hindrance between B and C rings and rendering certain pathways more feasible. Kinetic and molecular dynamics are essential to properly describe the membrane's lipid oxidation.

Biological Activity of Extracts of Red and Yellow Fruits of Cornus mas L.-An In Vitro Evaluation of Antioxidant Activity, Inhibitory Activity against α-Glucosidase, Acetylcholinesterase, and Binding Capacity to Human Serum Albumin.

Although extracts are broadly used in order to support the treatment of numerous diseases, only in a limited number of cases is the process of applying and establishing their mechanisms of action scientifically analyzed. Fruits of Cornelian cherry are an abundant source of iridoids, anthocyanins, flavonols and phenolic acids. The aim of the present study was to evaluate the in vitro bioactivity of red and yellow Cornelian cherry fruits' extracts. The biological potential of extracts, in a broad sense, involved antioxidant activity in relation to phosphatidylcholine liposomes, inhibitory ability against α-glucosidase and acetylcholinesterase enzymes, as well as interactions with human serum albumin. Studies showed that both extracts were more effective in protecting liposome membranes against free radicals produced by AAPH in an aqueous environment due to the fact that they can be better eliminated by the hydrophilic components of the extracts than those produced by UVB radiation. Extracts exhibited inhibitory activity against acetylcholinesterase and α-glucosidase, wherein loganic acid extract showed noncompetitive inhibition of the enzyme. Moreover, extracts binded to albumin mainly through hydrogen bonds and van der Waals forces. Taken together, red and yellow cherry fruits' extracts exhibit diverse biological properties and can be exploited as a source of natural therapeutic agents.

Anti-Diabetic and Antioxidant Activities of Red Wine Concentrate Enriched with Polyphenol Compounds under Experimental Diabetes in Rats.

We obtained red wine concentrate, which was enriched with natural polyphenolic compounds (PC concentrate). The main purpose was to study the hypoglycemic and antioxidant effects of the red wine concentrate, and its impact on key hematological parameters of rats with experimental diabetes mellitus. While administrating the red wine concentrate to rats with diabetes, partial recovering of glucose tolerance was promoted, as well as normalization of glycated hemoglobin level, an increase in the quantity of erythrocytes and hemoglobin concentration. PC concentrate had anti-radical effect, which was determined using 2,2-diphenyl-1-picrylhydrazylradical (DPPH) method and effectively inhibited oxidation of phosphatidylcholine liposomes, induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a free radical generator. It was also confirmed that PC concentrate had antioxidant properties in vivo. The contents of lipid peroxidation and protein oxidation products, the activity of catalase, and glutathione peroxidase (GPx) were increased in the plasma of rats with diabetes mellitus. At the same time, the activity of superoxide dismutase (SOD) was decreased. The concentrate of red wine had a corrective effect on investigated indicators and caused their normalization in plasma of diabetic animals.

Interaction of 4'-methylflavonoids with biological membranes, liposomes, and human albumin.

The aim of the study was to compare the impact of three synthesized chemical compounds from a group of methylated flavonoids, i.e. 2'-hydroxy-4-methylchalcone (3), 4'-methylflavanone (4), and 4'-methylflavone (5), on a red blood cell membranes (RBCMs), phosphatidylcholine model membranes (PC), and human serum albumin (HSA) in order to investigate their structure-activity relationships. In the first stage of the study, it was proved that all of the compounds tested do not cause hemolysis of red blood cells and, therefore, do not have a toxic effect. In biophysical studies, it was shown that flavonoids have an impact on the hydrophilic and hydrophobic regions of membranes (both RBCMs and PC) causing an increase in packing order of lipid heads and a decrease in fluidity, respectively. Whereas, on the one hand, the magnitude of these changes depends on the type of the compound tested, on the other hand, it also depends on the type of membrane. 4'-Methylflavanone and 4'-methylflavone are located mainly in the hydrophilic part of lipid membranes, while 2'-hydroxy-4-methylchalcone has a greater impact on the hydrophobic area. A fluorescence quenching study proved that compounds (3), (4) and (5) bind with HSA in a process of static quenching. The binding process is spontaneous whereas hydrogen bonding interactions and van der Waals forces play a major role in the interaction between the compounds and HSA.