Long-term clinical comparison of a resin-based composite and resin modified glass ionomer in the treatment of cervical caries lesions.

This 72-month study compared the clinical effectiveness of a resin-based composite (RBC) (Spectrum TPH3, Dentsply Sirona) with a resin-modified glass ionomer cement (RMGIC) (Riva Light Cure, SDI) in restoring cervical caries lesions (CCLs). Thirty-three patients, each with at least two CCLs, were enrolled. After caries removal, the dimensions of the cavities were recorded. In a split-mouth study design, a total of 110 restorations were randomly placed. Fifty-five restorations were placed with RBC using an etch-and-rinse adhesive system (Prime&Bond NT, Dentsply Sirona), while the remaining 55 were restored with RMGIC. The restorations were assessed at baseline, 6, 12, 18, 24, 36, 60, and 72 months according to modified USPHS criteria. Statistical analysis included Pearson Chi-square, Friedman tests, Kaplan Meier, and Logistic Regression analysis (p < 0.05). After 72 months, 47 restorations in 19 patients were evaluated (55% follow-up rate). Seventy-five percent of the RBC (n = 26) and 74% (n = 21) of the RMGIC restorations were fully retained. There were no significant differences between materials regarding retention and marginal adaptation (p > 0.05). Cavity dimensions, caries activity, and retention exhibited no correlation (p > 0.05). The increase in marginal staining in both groups over time was significant (p < 0.001). RMGIC restorations exhibited higher discoloration than RBC restorations (p = 0.014). At 72 months, three secondary caries lesions were detected in both restoration groups: two RMGIC and one RBC. There were no reports of sensitivity. After 72 months, both RBC and RMGIC restorations were clinically successful, with similar retention and marginal adaptation scores. However, it is noteworthy that RMGIC restorations tend to discoloration over time compared to RBC. The trial is registered in the database of "Clinical Trials". The registration number is NCT0372-2758, October 29, 2018.

Evaluation of Antioxidant Capacity, Anticholinergic and Antidiabetic Activities, and Phenolic Ingredients of Asphodelus aestivus by LC-MS/MS.

Herein, it was aimed to evaluate three different extracts of the plant Asphodelus aestivus in terms of their antioxidant capacity, total phenolic content, flavonoid profile, and anticholinergic and antidiabetic activity. In addition, the phenolic content of the A. aestivus extracts was determined by liquid chromatography-mass spectrometry/mass spectrometry. The results obtained in the antioxidant studies were checked against butylated hydroxyanisole, butylated hydroxytoluene, Trolox, and α-tocopherol antioxidants, which are reference standards. The half-maximal inhibition concentration (IC50 ) values of A. aestivus for 1,1-diphenyl-2-picryl-hydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) removal activity were 245.015-285.851 and 285.818-371.563 µg/mL, respectively. Then, the reducing impact of A. aestivus extracts was evaluated by the cupric ion (Cu2+ ), ferric ion (Fe3+ ), and Fe3+ -TPTZ reducing capabilities. Moreover, 0.058, 0.064, and 0.100 µg of gallic acid equivalent of phenolic and 0.500, 1.212, and 2.074 µg of quercetin equivalent of flavonoid contents were determined from 1 mg of ethanol, water, and water-ethanol extracts, respectively. For water-ethanol, ethanol, and water extracts of A. aestivus, IC50 values of 0.062±0.0001, 0.068±0.0002, and 0.090±0.0001 µg/mL against acetylcholinesterase, respectively, were calculated. In addition, against the enzyme α-glucosidase IC50 values of 16.376±0.2216, 18.907±0.3004, and 24.471±0.4929 µg/mL, respectively, were calculated. Extracts showed considerable biological activities thanks to the important molecules they contain.

Effect of a calcium phosphate-containing desensitizing agent on postoperative sensitivity: A split-mouth, randomized controlled study.

PURPOSE: To evaluate the effectiveness of a calcium phosphate-containing-desensitizer (Teethmate Desensitizer - TD), caries type, subject age, and preoperative hypersensitivity on postoperative sensitivity (POS) after composite restorations on deep or extremely deep lesions. METHODS: 50 subjects, having two teeth with deep or extremely deep caries, participated in this study. TD was applied randomly to one tooth of each participant, and all teeth were restored with composite resin (Filtek Z250). After 1 week, POS was evaluated according to NRS (numerical rating scale) and VAS (visual analogue scale) by using participant diaries. At 6 weeks, POS was assessed considering subjects' reports. The normality of data was analyzed with Shapiro-Wilk test. For analyses, Pearson's chi-squared test, Mann-Whitney U and the Wilcoxon Signed-Rank test were used, and the effect sizes (ES) were calculated (α= 0.05). RESULTS: 47 of the participants completed the 6-week study. There was a small effect size noted for TD for NRS and VAS (P> 0.05, ES < 0.30). Also, there was no statistically significant difference between POS and subject age (P= 0.294, ES= 0.161), type of caries (P= 0.680, ES= 0.042) and preoperative sensitivity (P= 1.000, ES= 0.138) after the first week. CLINICAL SIGNIFICANCE: Teethmate Desensitizer had no significant effect on postoperative sensitivity occurrence with respect to caries type, subject age, and existence of preoperative sensitivity. The application of Teethmate Desensitizer demonstrated no significant relieving effect on postoperative sensitivity in deep or extremely deep cavities.

Screening of Carbonic Anhydrase, Acetylcholinesterase, Butyrylcholinesterase, and α-Glycosidase Enzyme Inhibition Effects and Antioxidant Activity of Coumestrol.

Coumestrol (3,9-dihydroxy-6-benzofuran [3,2-c] chromenone) as a phytoestrogen and polyphenolic compound is a member of the Coumestans family and is quite common in plants. In this study, antiglaucoma, antidiabetic, anticholinergic, and antioxidant effects of Coumestrol were evaluated and compared with standards. To determine the antioxidant activity of coumestrol, several methods-namely N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD•+)-scavenging activity, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS•+)-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•)-scavenging activity, potassium ferric cyanide reduction ability, and cupric ion (Cu2+)-reducing activity-were performed. Butylated hydroxyanisole (BHA), Trolox, α-Tocopherol, and butylated hydroxytoluene (BHT) were used as the reference antioxidants for comparison. Coumestrol scavenged the DPPH radical with an IC50 value of 25.95 µg/mL (r2: 0.9005) while BHA, BHT, Trolox, and α-Tocopherol demonstrated IC50 values of 10.10, 25.95, 7.059, and 11.31 µg/mL, respectively. When these results evaluated, Coumestrol had similar DPPH•-scavenging effect to BHT and lower better than Trolox, BHA and α-tocopherol. In addition, the inhibition effects of Coumestrol were tested against the metabolic enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II), and α-glycosidase, which are associated with some global diseases such as Alzheimer's disease (AD), glaucoma, and diabetes. Coumestrol exhibited Ki values of 10.25 ± 1.94, 5.99 ± 1.79, 25.41 ± 1.10, and 30.56 ± 3.36 nM towards these enzymes, respectively.

Evaluation of the Antioxidant and Antiradical Properties of Some Phyto and Mammalian Lignans.

In this study, the antioxidant and antiradical properties of some phyto lignans (nordihydroguaiaretic acid, secoisolariciresinol, secoisolariciresinol diglycoside, and α-(-)-conidendrin) and mammalian lignans (enterodiol and enterolactone) were examined by different antioxidant assays. For this purpose, radical scavenging activities of phyto and mammalian lignans were realized by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS•+) scavenging assay and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assay. Additionally, the reducing ability of phyto and mammalian lignans were evaluated by cupric ions (Cu2+) reducing (CUPRAC) ability, and ferric ions (Fe3+) and [Fe3+-(TPTZ)2]3+ complex reducing (FRAP) abilities. Also, half maximal inhibitory concentration (IC50) values were determined and reported for DPPH• and ABTS•+ scavenging influences of all of the lignan molecules. The absorbances of the lignans were found in the range of 0.150-2.320 for Fe3+ reducing, in the range of 0.040-2.090 for Cu2+ reducing, and in the range of 0.360-1.810 for the FRAP assay. On the other hand, the IC50 values of phyto and mammalian lignans were determined in the ranges of 6.601-932.167 µg/mL for DPPH• scavenging and 13.007-27.829 µg/mL for ABTS•+ scavenging. In all of the used bioanalytical methods, phyto lignans, as secondary metabolites in plants, demonstrated considerably higher antioxidant activity compared to that of mammalian lignans. In addition, it was observed that enterodiol and enterolactone exhibited relatively weaker antioxidant activities when compared to phyto lignans or standard antioxidants, including butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), Trolox, and α-tocopherol.

Synthesis and biological evaluation of some 1-naphthol derivatives as antioxidants, acetylcholinesterase, and carbonic anhydrase inhibitors.

A series of some naphthol derivatives 4a-f, 5a,f, 6a, and 7a,b (six novel ones: 4c,d, 5a, 6a, 7a,b) bearing F, Cl, Br, OMe, and dioxole substituents at different positions of the aromatic rings was designed, synthesized, and characterized. The naphthol derivatives were synthesized in three steps, namely the addition reaction of furan via Diels-Alder cycloaddition reaction, copper(II) trifluoromethanesulfonate (Cu(OTf)2 )-catalyzed aromatization reaction, and the bromination reaction, respectively. The structures of the newly obtained compounds (4c,d, 5a, 6a, 7a,b) were characterized by spectroscopic techniques. In addition, some biological activity studies were investigated under in vitro conditions. Inhibition studies of these compounds were performed on human carbonic anhydrase (hCA) I and II isoenzymes purified from human erythrocytes as a biological evaluation. Moreover, their potential antioxidant and antiradical activities were studied by analytical methods like ABTS•+ and DPPH• scavenging, and it was determined that some molecules showed good activity. Also, inhibition of acetylcholinesterase (AChE), which is a marker of many degenerative neurological diseases, was tested and the results were discussed. Excellent enzyme inhibition results were recorded for most of the molecules. These 1-naphthol derivatives were found as effective inhibitors for hCA I, hCA II, and AChE with K i values ranging from 0.034 ± 0.54 to 0.724 ± 0.18 µM for hCA I, 0.172 ± 0.02 to 0.562 ± 0.21 µM for hCA II, and 0.096 ± 0.01 to 0.177 ± 0.02 µM for AChE.

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.

Acetylcholinesterase and carbonic anhydrase inhibitory properties of novel urea and sulfamide derivatives incorporating dopaminergic 2-aminotetralin scaffolds.

In the present study a series of urea and sulfamide compounds incorporating the tetralin scaffolds were synthesized and evaluated for their acetylcholinesterase (AChE), human carbonic anhydrase (CA, EC 4.2.1.1) isoenzyme I, and II (hCA I and hCA II) inhibitory properties. The urea and their sulfamide analogs were synthesized from the reactions of 2-aminotetralins with N,N-dimethylcarbamoyl chloride and N,N-dimethylsulfamoyl chloride, followed by conversion to the corresponding phenols via O-demethylation with BBr3. The novel urea and sulfamide derivatives were tested for inhibition of hCA I, II and AChE enzymes. These derivatives exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values of 2.61-3.69nM against hCA I, 1.64-2.80nM against hCA II, and in the range of 0.45-1.74nM against AChE. In silico techniques such as, atomistic molecular dynamics (MD) and molecular docking simulations, were used to understand the scenario of the inhibition mechanism upon approaching of the ligands into the active site of the target enzymes. In light of the experimental and computational results, crucial amino acids playing a role in the stabilization of the enzyme-inhibitor adducts were identified.

Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase.

A series of carbamate derivatives were synthesized and their carbonic anhydrase I and II isoenzymes and acetylcholinesterase enzyme (AChE) inhibitory effects were investigated. All carbamates were synthesized from the corresponding carboxylic acids via the Curtius reactions of the acids with diphenyl phosphoryl azide followed by addition of benzyl alcohol. The carbamates were determined to be very good inhibitors against for AChE and hCA I, and II isoenzymes. AChE inhibition was determined in the range 0.209-0.291 nM. On the other hand, tacrine, which is used in the treatment of Alzheimer's disease possessed lower inhibition effect (Ki: 0.398 nM). Also, hCA I and II isoenzymes were effectively inhibited by the carbamates, with inhibition constants (Ki) in the range of 4.49-5.61 nM for hCA I, and 4.94-7.66 nM for hCA II, respectively. Acetazolamide, which was clinically used carbonic anhydrase (CA) inhibitor demonstrated Ki values of 281.33 nM for hCA I and 9.07 nM for hCA II. The results clearly showed that AChE and both CA isoenzymes were effectively inhibited by carbamates at the low nanomolar levels.

Synthesis of N-alkyl (aril)-tetra pyrimidine thiones and investigation of their human carbonic anhydrase I and II inhibitory effects.

Tetrahydropyrimidine thiones, which are cyclic thiocarbamides derivatives, were synthesised from thiourea, ß-diketones and substituted benzaldehydes. A tautomeric form of these derivatives incorporates the thiol functionality, which is known to interact with metal ions from metalloenzymes active sites, such as the carbonic anhydrases (CAs, EC 4.2.1.1) among others. This is a superfamily of widespread enzymes, which catalyses a crucial biochemical reaction, the reversible hydration of carbon dioxide to bicarbonate and protons (H(+)). The newly synthesised N-alkyl (aril)-tetrahydropyrimidine thiones were tested for inhibition of the cytosolic human isoforms I and II (hCA I and II). Both isoforms were effectively inhibited by the newly synthesised thiones. Ki values were in the range of 218.5 ± 23.9-261.0 ± 41.5 pM for hCA I, and of 181.8 ± 41.9-273.6 ± 41.4 pM for hCA II, respectively. This under-investigated class of derivatives may bring interesting insights in the field of non-sulphonamide CA inhibitors.

The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acids derivatives and determination of their inhibition properties against human carbonic anhydrase I and II isoenzymes.

The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acid (4) derivatives containing structural characteristics that can be used for the synthesis of several active molecules, is presented. Some of the butenoic acid derivatives (4a, 4c, 4e, 4i, 4j, 4k) are synthesized following literature procedures and at the end of the reaction. In addition, structures of all synthesized derivatives (4a-4m) were determined by (1)H-NMR, (13)C-NMR and IR spectroscopy. Carbonic anhydrase is a metalloenzyme involved in many crucial physiologic processes as it catalyzes a simple but fundamental reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Significant results were obtained by evaluating the enzyme inhibitory activities of these derivatives against human carbonic anhydrase hCA I and II isoenzymes (hCA I and II). Butenoic acid derivatives (4a-4m) strongly inhibited hCA I and II with Kis in the low nanomolar range of 1.85 ± 0.58 to 5.04 ± 1.46 nM against hCA I and in the range of 2.01 ± 0.52 to 2.94 ± 1.31 nM against hCA II.

The human carbonic anhydrase isoenzymes I and II inhibitory effects of some hydroperoxides, alcohols, and acetates.

The carbonic anhydrases (CAs, EC 4.2.1.1) represent a superfamily of widespread enzymes, which catalyze a crucial biochemical reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, a series of hydroperoxides, alcohols, and acetates were tested for the inhibition of the cytosolic hCA I and II isoenzymes. These compounds inhibited both hCA isozymes in the low nanomolar ranges. These compounds were good hCA I inhibitors (Kis in the range of 24.93-97.99 nM) and hCA II inhibitors (Kis in the range of 26.04-68.56 nM) compared to acetazolamide as CA inhibitor (Ki: 34.50 nM for hCA I and Ki: 28.93 nM for hCA II).

The effects of some avermectins on bovine carbonic anhydrase enzyme.

Avermectins are effective agricultural pesticides and antiparasitic agents that are widely employed in the agricultural, veterinary and medical fields. The aim of this study was to investigate the inhibitory effects of selected avermectins including abamectin, doramectin, emamectin, eprinomectin, ivermectin and moxidectin that are used as drugs against a wide variety of internal and external mammalian parasites, on the carbonic anhydrase enzyme (CA, EC 4.2.1.1.) purified from fresh bovine erythrocyte. CA catalyses the rapid interconversion of carbon dioxide (CO2) and water (H2O) to bicarbonate ([Formula: see text]) and protons (H(+)) and regulate the acidity of the local tissues. Bovine erythrocyte CA (bCA) enzyme was purified by Sepharose-4B affinity chromatography with a yield of 21.96% and 262.7-fold purification. The inhibition results obtained from this study showed Ki values of 9.73, 17.39, 20.43, 13.39, 16.44 and 17.73 nM for abamectin, doramectin, emamectin, eprinomectin, ivermectin and moxidectin, respectively. However, acetazolamide, well-known clinically established CA inhibitor, possessed a Ki value of 27.68 nM.

Antioxidant, antiradical, and anticholinergic properties of cynarin purified from the Illyrian thistle (Onopordum illyricum L.).

Cynarin is a derivative of hydroxycinnamic acid and it has biologically active functional groups constituent of some plants and food. We elucidated the antioxidant activity of cynarin by using different in vitro condition bioanalytical antioxidant assays like DMPD(•+), ABTS(•+), O2(•-), DPPH(•) and H2O2 scavenging effects, the total antioxidant influence, reducing capabilities, Fe(2+) chelating and anticholinergic activities. Cynarin demonstrated 87.72% inhibition of linoleic acid lipid peroxidation at 30 µg/mL concentration. Conversely, some standard antioxidants like trolox, α-tocopherol, butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA) exhibited inhibitions of 90.32, 75.26, 97.61, 87.30%, and opponent peroxidation of linoleic acid emulsion at the identical concentration, seriatim. Also, cynarin exhibited effective DMPD(•+), ABTS(•+), O2(•-), DPPH(•), and H2O2 scavenging effects, reducing capabilities and Fe(2+) chelating effects. On the contrary, IC50 and K(i) parameters of cynarin for acetylcholinesterase enzyme inhibition were determined as 243.67 nM (r(2): 0.9444) and 39.34 ± 13.88 nM, respectively. This study clearly showed that cynarin had marked antioxidant, anticholinergic, reducing ability, radical-scavenging, and metal-binding activities.