Synthesis and Inhibitor Effect Novel Alkoxymethyl Derivatives of Dihetero Cycloalkanes on Carbonic Anhydrase and Acetylcholinesterase.

1,3-Diheterocycloalkanes derivatives are important starting materials in fine organic synthesis. These compounds can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. The paper is focused on synthesis and study of alkoxymethyl derivatives of diheterocycloalkanes (M1-M15) and inhibition effect on carbonic anhydrase and acetylcholinesterase. The structures of compounds were confirmed by 1H and 13C NMR spectroscopy. Also, in this study alkoxymethyl derivatives of diheterocycloalkanes were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). The results demonstrated that all these compounds exhibited potent inhibitory effects on all the target enzymes, surpassing the standard inhibitors, as evidenced by their IC50 and Ki values. The Ki values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 1.02±0.17-8.38±1.02, 15.30±3.15-58.14±5.17 and 24.05±3.70-312.94±27.24 nM, respectively.

Potential antioxidant, anticholinergic, antidiabetic and antiglaucoma activities and molecular docking of spiraeoside as a secondary metabolite of onion (Allium cepa).

Onion contains many dietary and bioactive components including phenolics and flavonoids. Spiraeoside (quercetin-4-O-ß-D-glucoside) is one of the most putative flavonoids in onion. Several antioxidant techniques were used in this investigation to assess the antioxidant capabilities of spiraeoside, including 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·) scavenging, N,N-dimethyl-p-phenylenediamine radical (DMPD•+) scavenging, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS•+) scavenging activities, cupric ions (Cu2+) reducing and potassium ferric cyanide reduction abilities. In contrast, the water-soluble α-tocopherol analogue trolox and the conventional antioxidants butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and α-tocopherol were utilized as the standards for evaluation. Spiraeoside scavenged the DPPH radicals an IC50 of 28.51 µg/mL (r2: 0.9705) meanwhile BHA, BHT, trolox, and α-tocopherol displayed IC50 of 10.10 µg/mL (r2: 0.9015), 25.95 µg/mL (r2: 0.9221), 7.059 µg/mL (r2: 0.9614) and 11.31 µg/mL (r2: 0.9642), accordingly. The results exhibited that spiraeoside had effects similar to BHT, but less potent than α-tocopherol, trolox and BHA. Also, inhibitory effects of spiraeoside were evaluated toward some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II) and α-glycosidase, which are related to a number of illnesses, such as Alzheimer's disease (AD), diabetes mellitus and glaucoma disorder. Spiraeoside exhibited IC50 values of 4.44 nM (r2: 0.9610), 7.88 nM (r2: 0.9784), 19.42 nM (r2: 0.9673) and 29.17 mM (r2: 0.9209), respectively against these enzymes. Enzyme inhibition abilities were compared to clinical used inhibitors including acetazolamide (for CA II), tacrine (for AChE and BChE) and acarbose (for α-glycosidase). Spiraeoside demonstrated effective antioxidant, anticholinergic, antidiabetic and antiglaucoma activities. With these properties, it has shown that Spiraeoside has the potential to be a medicine for some metabolic diseases.

Comprehensive Metabolite Profiling of Berdav Propolis Using LC-MS/MS: Determination of Antioxidant, Anticholinergic, Antiglaucoma, and Antidiabetic Effects.

Propolis is a complex natural compound that honeybees obtain from plants and contributes to hive safety. It is rich in phenolic and flavonoid compounds, which contain antioxidant, antimicrobial, and anticancer properties. In this study, the chemical composition and antioxidant activities of propolis were investigated; ABTS•+, DPPH• and DMPD•+ were prepared using radical scavenging antioxidant methods. The phenolic and flavonoid contents of propolis were 53 mg of gallic acid equivalent (GAE)/g and 170.164 mg of quercetin equivalent (QE)/g, respectively. The ferric ion (Fe3+) reduction, CUPRAC and FRAP reduction capacities were also studied. The antioxidant and reducing capacities of propolis were compared with those of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and Trolox reference standards. The half maximal inhibition concentration (IC50) values of propolis for ABTS•+, DPPH• and DMPD•+ scavenging activities were found to be 8.15, 20.55 and 86.64 µg/mL, respectively. Propolis extract demonstrated IC50 values of 3.7, 3.4 and 19.6 µg/mL against α-glycosidase, acetylcholinesterase (AChE) and carbonic anhydrase II (hCA II) enzyme, respectively. These enzymes' inhibition was associated with diabetes, Alzheimer's disease (AD) and glaucoma. The reducing power, antioxidant activity and enzyme inhibition capacity of propolis extract were comparable to those demonstrated by the standards. Twenty-eight phenolic compounds, including acacetin, caffeic acid, p-coumaric acid, naringenin, chrysin, quinic acid, quercetin, and ferulic acid, were determined by LC-MS/MS to be major organic compounds in propolis. The polyphenolic antioxidant-rich content of the ethanol extract of propolis appears to be a natural product that can be used in the treatment of diabetes, AD, glaucoma, epilepsy, and cancerous diseases.

Sahlep (Dactylorhiza osmanica): Phytochemical Analyses by LC-HRMS, Molecular Docking, Antioxidant Activity, and Enzyme Inhibition Profiles.

Studies have shown an inverse correlation among age-related illnesses like coronary heart disease and cancer and intake of fruit and vegetable. Given the probable health benefits of natural antioxidants from plants, research on them has increased. Dactylorhiza osmanica is consumed as a food and traditional medicine plant in some regions of Turkey, so evaluation of the biological ability of this species is important. In this study, the amount of phenolic content (LC-HRMS), antioxidant activities and enzyme inhibitory properties of an endemic plant, D. osmanica, were investigated. The antioxidant capacities of an ethanol extract of D. osmanica aerial parts (EDOA) and roots (EDOR) were evaluated with various antioxidant methods. Additionally, the enzyme inhibitory effects of EDOA and EDOR were examined against acetylcholinesterase (AChE), α-glycosidase, and α-amylase enzymes, which are associated with common and global Alzheimer's disease and diabetes mellitus. The IC50 values of EDOA against the enzymes were found to be 1.809, 1.098, and 0.726 mg/mL, respectively; and the IC50 values of EDOR against the enzymes were found to be 2.466, 0.442, and 0.415 mg/mL, respectively. Additionally, LC-HRMS analyses revealed p-Coumaric acid as the most plentiful phenolic in both EDOA (541.49 mg/g) and EDOR (559.22 mg/g). Furthermore, the molecular docking interaction of p-coumaric acid, quercitrin, and vanillic acid, which are the most plentiful phenolic compounds in the extracts, with AChE, α-glucosidase, and α-amylase, were evaluated using AutoDock Vina software. The rich phenolic content and the effective antioxidant ability and enzyme inhibition potentials of EDOA and EDOR may support the plant's widespread food and traditional medicinal uses.

Antioxidant, Antidiabetic, Anticholinergic, and Antiglaucoma Effects of Magnofluorine.

Magnofluorine, a secondary metabolite commonly found in various plants, has pharmacological potential; however, its antioxidant and enzyme inhibition effects have not been investigated. We investigated the antioxidant potential of Magnofluorine using bioanalytical assays with 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD•+), and 1,1-diphenyl-2-picrylhydrazyl (DPPH•) scavenging abilities and K3[Fe(CN)6] and Cu2+ reduction abilities. Further, we compared the effects of Magnofluorine and butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), α-Tocopherol, and Trolox as positive antioxidant controls. According to the analysis results, Magnofluorine removed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals with an IC50 value of 10.58 µg/mL. The IC50 values of BHA, BHT, Trolox, and α-Tocopherol were 10.10 µg/mL, 25.95 µg/mL, 7.059 µg/mL, and 11.31 µg/mL, respectively. Our results indicated that the DPPH· scavenging effect of Magnofluorine was similar to that of BHA, close to that of Trolox, and better than that of BHT and α-tocopherol. The inhibition effect of Magnofluorine was examined against enzymes, such as acetylcholinesterase (AChE), α-glycosidase, butyrylcholinesterase (BChE), and human carbonic anhydrase II (hCA II), which are linked to global disorders, such as diabetes, Alzheimer's disease (AD), and glaucoma. Magnofluorine inhibited these metabolic enzymes with Ki values of 10.251.94, 5.991.79, 25.411.10, and 30.563.36 nM, respectively. Thus, Magnofluorine, which has been proven to be an antioxidant, antidiabetic, and anticholinergic in our study, can treat glaucoma. In addition, molecular docking was performed to understand the interactions between Magnofluorine and target enzymes BChE (D: 6T9P), hCA II (A:3HS4), AChE (B:4EY7), and α-glycosidase (C:5NN8). The results suggest that Magnofluorine may be an important compound in the transition from natural sources to industrial applications, especially new drugs.

Comprehensive evaluation of Reseda lutea L. (Wild Mignonette) and 7 isolated flavonol glycosides: determination of antioxidant activity, anti-Alzheimer, antidiabetic and cytotoxic effects with in vitro and in silico methods.

In this study, anticholinergic, antidiabetic, antioxidant and cytotoxic activities of Reseda lutea L. (R. lutea) were determined. Ethanol extracts of R. lutea (EERL) and water extract of R. lutea (WERL) were prepared for biochemical analysis. The antioxidant capacities of EERL and WERL were evaluated with 6 different methods. In addition, acetylcholinesterase (AChE), α-amylase and α-glycosidase enzyme inhibition by EERL were measured. According to the results, EERL exhibited high inhibition effects against α-amylase, α-glycosidase and AChE enzymes. The IC50 values of EERL against AChE (2.21 µg/mL), α-glycosidase (1.38 µg/mL), and α-amylase (0.11 µg/mL) were determined. Also, high cytotoxic effect of EERL was observed on human lung cancer cell lines (A549) with an IC50 value of 3.58 ± 1.10 µg/mL. The affinities of 7 kaempferol and isorhamnetin rhamnopyranoside molecules, previously isolated from R. lutea, for AChE, α-amylase and, α-glycosidase were determined by molecular docking studies. Molecular docking results supported the in vitro results of the study. The results showed that the aerial parts of R. lutea have effective antioxidant, anticholinergic, antidiabetic and cytotoxic activities. This research will form the basis for further studies about R. lutea usage for drug development.

Antidiabetic, anticholinergic and antioxidant activities of aerial parts of shaggy bindweed (Convulvulus betonicifolia Miller subsp.) - profiling of phenolic compounds by LC-HRMS.

In order to evaluate the antioxidant activity of evaporated ethanolic extract (EESB) and lyophilized water extract (WESB) of Shaggy bindweed (Convulvulus betonicifolia Mill. Subs), some putative antioxidant methods such as DPPH· scavenging activity, ABTS•+ scavenging effect, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+) binding activities were separately performed. Also, ascorbic acid, α-tocopherol and BHT were used as the standard compounds. Additionally, some phenolic compounds that responsible for antioxidant abilities of EESB and WESB were screened by liquid chromatography-high resolution mass spectrometry (LC-HRMS). At the same concentration, EESB and WESB demonstrated effective antioxidant abilities when compared to standards. In addition, EESB demonstrated IC50 values of 1.946 µg/mL against acetylcholinesterase (AChE), 0.815 µg/mL against α-glycosidase and 0.675 µg/mL against α-amylase enzymes.

LC-HRMS Profiling and Antidiabetic, Anticholinergic, and Antioxidant Activities of Aerial Parts of Kinkor (Ferulago stellata).

Kinkor (Ferulago stellata) is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kinkor (Ferulago stellata), some putative antioxidant methods such as DPPH· scavenging activity, ABTS•+ scavenging activity, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and α-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kinkor (Ferulago stellata) were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kinkor (Ferulago stellata) demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kinkor (Ferulago stellata) demonstrated IC50 values of 1.772 µg/mL against acetylcholinesterase (AChE), 33.56 ± 2.96 µg/mL against α-glycosidase, and 0.639 µg/mL against α-amylase enzyme respectively.

Nephroprotective effect of Ferulago angulata flowers on N-nitrosodimethylamine-induced nephrotoxicity in rats and its phytochemical profile.

The present study was designed to assess the phytochemical content of Ferulago angulata (FA) and possible in vivo nephroprotective effect of FA administration on trace elements, minerals, MDA and GSH in kidney and liver tissue samples, serum vitamin (α-tocopherol, retinol, cholecalciferol, phylloquinone), TSA, and LSA in a rat model of DMN-induced nephrotoxicity. In the study, Wistar albino rats were assigned to six groups: Control (0.9% NaCl), (DMN 10 mg/kg), (FA 150 mg/kg), (DMN + FA 150 mg/kg), (FA 300 mg/kg), and (DMN + FA 300 mg/kg). Rats were intraperitoneally given DMN for the first 7 days. Renal injury caused by DMN was proved by the histopathological alterations. The FA (300 mg/kg) treatment significantly normalized Se, Cr, Ca levels in liver and Co level in kidney tissue samples. These observed positive effects are due to the phytochemical content of the plant. The flower extract of FA (300 mg/kg) can be used for the prevention of kidney damage. PRACTICAL APPLICATIONS: Ferulago angulata flowers are used in traditional medicine for treat kidney and liver digestive system diseases. This species is endemic taxa of the family Apiaceae, which has been used both as food and therapeutics because of their phytochemical composition. In this study, the phenolic characterization of FA flower was used to a new RP-HPLC method, as well as the biological activity of FA flower and possible in vivo nephroprotective effect of FA flowers on trace elements, minerals, MDA and GSH in kidney and liver tissue samples and vitamins, TSA, and LSA in serum samples a rat model of DMN-induced nephrotoxicity. It was found that high level of phenolic compounds (chlorogenic acid, vanillic acid, 2-hydroxycinnamic acid) present in the flower extract of F. angulata has positive effects and antioxidant properties. Due to its phenolic content, FA flower extract could protect for kidney damage and can be used as antioxidants in the food additive and pharmaceutical industry.

Antioxidant properties of Ferulago angulata and its hepatoprotective effect against N-nitrosodimethylamine-induced oxidative stress in rats.

CONTEXT: Ferulago angulata (Schlecht.) Boiss. (Apiaceae) (FASB) is used to treat liver diseases and has been used both as food and therapeutics by many cultures for thousands of years because of the natural antioxidant compounds. OBJECTIVE: This study determines antioxidant properties of FASB flowers, the levels of minerals and vitamins, and also, evaluates the hepatoprotective effect of flowers against N-nitrosodimethylamine (NDMA) induced on liver tissue by assessing antioxidant enzymes and histopathological parameters in Wistar albino rats. MATERIALS AND METHODS: In the study, the rats were divided into six groups of ten. Control, untreated animals were given 0.9% NaCl. Rats were intraperitoneally given NDMA (10 mg/kg) for the first 7 days. FASB methanol extract (150 and 300 mg/kg) was administered orally for 21 days. RESULTS: α-Tocopherol, retinol, ascorbic acid, total antioxidant activity, phenolic and flavonoid contents of FASB were 0.70 ± 0.13, 0.29 ± 0.03 µg/g, 139.32 ± 7.06 µg/100 g, 171.61 ± 6.05 mM ascorbic acid/g, 90.47 ± 4.11 mg GA/g and 37.39 ± 2.85 mg QE/g. DPPH and hydroxyl radical scavenging activity was obtained IC50 67.34 ± 4.14 and 64.87 ± 4.68 µg/mL, respectively. DISCUSSION AND CONCLUSION: The results of the study indicated that FASB flowers contain high levels of vitamins, minerals, total antioxidant activity, phenolics and flavonoids. Due to the positive effect on significant changes in antioxidant enzymes of liver tissue and histopathological examination, it is thought that the plant could be used as a hepatoprotective.

Chemical Composition and Antioxidant Activity of Two Wild Edible Mushrooms from Turkey.

The purpose of this study was to determine the antioxidant and antiradical activities in methanol extracts of two edible mushrooms from Turkey, Agaricus urinascens (Jul. Schäff. & F.H. Møller) Singer and Volvopluteus gloiocephala (DC.) Vizzini, Contu & Justo, as well as to examine trace elements (Cu, Zn, Fe, Mn, Co, Cr, Cd, Pb), minerals (Mg, Ca, K, Na) and vitamin C content. The levels of trace elements and minerals were determined by inductively coupled plasma atomic emission spectroscopy. Vitamin C and antioxidant properties were measured with a spectrophotometer. According to the results, total antioxidant activity and phenolic and flavonoid contents of A. urinascens and V. gloiocephala were 67.53 ± 2.54 mM ascorbic acid/g and 31.68 ± 2.27 mM ascorbic acid/g, 6.88 ± 0.31 mg GA/g and 5.22 ± 0.53 mg GA/g, and 3.80 ± 0.04 mg QE/g and 2.60 ± 0.20 mg QE/g, respectively. The findings of this study indicated that methanol extract of A. urinascens has a significant antioxidant activity and contents of total phenolic and flavonoid compounds. However, V. gloiocephala contains high levels of Ca, Cr, Fe, K, Mg, Mn, and Na, whereas A. urinascens contains higher levels of Cd, Co, Cu, Pb, and Zn than that of V. gloiocephala. Some trace elements that are in the compound of macrofungi may contribute the antioxidant capacity of macrofungi. A. urinascens has the ability to accumulate some heavy metals that prevent environmental metal pollution and can be used as a biomonitor. A. urinascens is expected to be used as an antioxidant in future studies of experimental animal models, against free radicals generated in response to oxidative stress.

Trace element status of chronic renal patients undergoing hemodialysis.

The purpose of this study was to examine the status of trace elements (Cu, Zn, and Fe) and minerals (Mg, K, Na, and Cl) and the level of biochemical parameters (urea, creatinine, total protein, albumin, and glucose) in hemodialysis (HD) patients. This study included 30 HD patients (25 men and 5 women) aged 52.12 +/- 3.13 years and 30 healthy subjects (23 men and 7 women) aged 51.64 +/- 2.22 years. This study investigated the status of trace elements and minerals in HD patients. It was found that the total HD patients (before and after dialysis) had statistically lower Zn and albumin in the after-dialysis group K and Cl levels and higher Mg, creatinine, and urea in the before-dialysis group K and in the after-dialysis group glucose levels than those of the controls. It was determined that the results might be helpful in monitoring patients with renal failure in terms of insufficiency or excess of trace elements and minerals. There was positive correlation for Mg-K (r = 0.64; p = 0.001), creatinine-urea (r = 0.59; p = 0.001), K-urea (r = 0.56; p = 0.001), K-creatinine (r = 0.52; p = 0.003), Mg-creatinine (r = 0.47; p = 0.008), Zn-albumin (r = 0.40; p = 0.028), and Zn-creatinine (r = 0.40; p = 0.031) in the before-dialysis session. There was also positive correlation for creatinine-urea (r = 0.56; p = 0.001), K-urea (r = 0.39; p = 0.035), and Mg-creatinine (r = 0.38; p = 0.041) in the after-analysis session. As a result of the analysis of regression between serum levels of albumin and zinc in total HD patients, the use of the level of albumin might be a suitable choice in determining zinc deficiency resulting from the decrease in the level of zinc in parallel to that of albumin. The results also suggest that the relationship between creatinine and K, Mg, and Zn could be ascribed to the loss of renal function.