Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin.

Taxifolin, also known as dihydroquercetin, is a flavonoid commonly found in plants. Carbonic anhydrase (CA, EC 4.2.1.1) plays an important role in many critical physiological events including carbon dioxide (CO2)/bicarbonate (HCO3(-)) respiration and pH regulation. There are 16 known CA isoforms in humans, of which human hCA isoenzymes I and II (hCA I and II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of taxifolin against the slow cytosolic isoenzyme hCA I, and the ubiquitous and dominant rapid cytosolic isoenzyme hCA II were studied. Taxifolin, as a naturally bioactive flavonoid, has a K(i) of 29.2 nM against hCA I, and 24.2 nM against hCA II. For acetylcholinesterase enzyme (AChE) inhibition, K(i) parameter of taxifolin was determined to be 16.7 nM. These results clearly show that taxifolin inhibited both CA isoenzymes and AChE at the nM levels.

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.

Spirobisnaphthalenes effectively inhibit carbonic anhydrase.

This study explores the correlation between human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II (hCA I, II) and the inhibitory features of some spirobisnaphthalene derivatives. A group of spirobisnaphthalenes was synthesized and their hCA I and II inhibitory effects was investigated. The Ki values were similar for both CA isoenzymes, the compounds showing good inhibitory activity. Ki values ranged between 1.60 and 460.42 µM for hCA I and between 0.39 and 419.42 µM for hCA II, respectively. The spirobisnaphthalenes derivatives might be useful for designing CA inhibitors belonging to novel chemotypes compared to the highly investigated sulfonamides, sulfamates or coumarins.

Antioxidant activity of taxifolin: an activity-structure relationship.

Taxifolin is a kind of flavanonol, whose biological ability. The objectives of this study were to investigate the antioxidants and antiradical activities of taxifolin by using different in vitro bioanalytical antioxidant methods including DMPD√(+), ABTS√(+), [Formula: see text], and DPPH√-scavenging effects, the total antioxidant influence, reducing capabilities, and Fe(2+)-chelating activities. Taxifolin demonstrated 81.02% inhibition of linoleic acid emulsion peroxidation at 30 µg/mL concentration. At the same concentration, standard antioxidants including trolox, α-tocopherol, BHT, and BHA exhibited inhibitions of linoleic acid emulsion as 88.57, 73.88, 94.29, and 90.12%, respectively. Also, taxifolin exhibited effective DMPD√(+), ABTS√(+), [Formula: see text], and DPPH√-scavenging effects, reducing capabilities, and Fe(2+)-chelating effects. The results obtained from this study clearly showed that taxifolin had marked antioxidant, reducing ability, radical scavenging and metal-chelating activities. Also, this study exhibits a scientific shore for the significant antioxidant activity of taxifolin and its structure-activity insight.

Synthesis of 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene Derivatives and Evaluations of Their Carbonic Anhydrase Isoenzymes Inhibitory Effects.

Rearrangement of 1,6-bis(3,4-dimethoxyphenyl)hexane-1,6-dione (8) gave two isomeric products having cyclopentene moiety. Starting from the major product (3,4-dimethoxyphenyl)[2-(3,4-dimethoxyphenyl)cyclopent-1-en-1-yl]methanone (11), eight new compounds (16-23) were obtained by the reactions such as reduction (by catalytic hydrogenation and NaBH4 ), nitration, 1,4-addition, bromination, and esterification reactions. Carbonic anhydrases (CA, E.C.4.2.1.1) are ubiquitous metalloenzymes present in almost all living organism that catalyze a simple reaction, the conversion of carbon dioxide (CO2 ) and water (H2 O) to bicarbonate ion (HCO3 (-) ) and a proton (H(+) ). CA isoenzymes I and II (hCA I and II) inhibition effects of synthesized eleven new and four known compounds (8-13 and 15-23) were investigated. Inhibition studies of the hCA I and II with 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene derivatives revealed that they possess effective inhibitory potency. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene derivatives with Ki s in the range of 313.16-1537.00 nm against hCA I and in the range of 228.31-1927.31 nm against hCA II, respectively.

Carbonic anhydrase and acetylcholinesterase inhibitory effects of carbamates and sulfamoylcarbamates.

Carbonic anhydrases (CA), as a family of metalloenzymes, are found in almost every type of tissue and play an important role in catalyzing the equilibration of carbon dioxide and carbonic acid. In this study, a series of carbamate derivative was synthesized, and their inhibition effects on hCA I, hCA II and acetylcholinesterase (AChE) enzymes were investigated. They were determined to be very good inhibitor against for both isoenzymes (hCA I and hCA II) and AChE. The hCA I and hCA II were effectively inhibited by the carbamate derivatives, with inhibition constants (Ki) in the range of 194.4-893.5 nM (for hCA I) and 103.9-835.7 nM (for hCA II). On the other hand, Ki parameters of these compounds for AChE enzyme inhibition were determined in the range of 12.0-61.3 nM. The results clearly showed that both CA isoenzymes and AChE were inhibited by carbamate derivatives at the nM levels.

Synthesis and carbonic anhydrase isoenzymes inhibitory effects of brominated diphenylmethanone and its derivatives.

Known and novel derivatives including CO, Br, and OH (benzylic and phenolic), and the corresponding benzylic alcohols of (3,4-dimethoxyphenyl)(2,3,4-dimethoxyphenyl)methanone were synthesized, and their inhibitory effects on the carbonic anhydrase (CA) isoenzymes I and II were investigated. CAs are the metalloenzymes catalyzing the reversible hydration of carbon dioxide (CO2 ) to bicarbonate (HCO3 (-) ). The inhibitory effects of diphenylmethanone derivatives 5-18 were tested on human CA (hCA, EC 4.2.1.1) isoenzymes (hCA I and hCA II) and they inhibited both isoenzymes at micromolar levels. Compounds 5 and 10 were found to be the best inhibitors against both CA isoenzymes. According to our data, compound 10 was the best inhibitor for isoenzyme hCA I (IC50 = 3.48 µM, Ki = 2.19 µM) whereas compound 5 was found to be the best inhibitor for isoenzyme hCA II (IC50 = 1.33 µM, Ki = 2.09 µM). Probably, stable conformations of 5 and 10 are more convenient for interaction with CA isoenzymes than those of the other compounds.

Synthesis and carbonic anhydrase isoenzymes I and II inhibitory effects of novel benzylamine derivatives.

Synthesis and carbonic anhydrase inhibitory properties of novel diarylmethylamines 22-25 and sulfonamide derivatives 26-28 were investigated. Acylation of methoxy-substituted benzenes with benzene carboxylic acids, reduction of ketones with NaBH4, conversion of alcohols to azides, Pd-C catalyzed hydrogenation of azides afforded title compounds 22-25. Compounds 22, 24 and 25 were converted to sulfonamide derivatives 26-28 with MeSO2Cl. The inhibitory effects of novel benzylamine derivatives 22-28 were tested on human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes hCA I and II. The results demonstrated that compound 28 was found to be the best inhibitor against both hCA I (Ki: 3.68 µM) and hCA II (Ki: 9.23 µM).

Carbonic anhydrase inhibitory properties of novel sulfonamide derivatives of aminoindanes and aminotetralins.

Six sulfonamides derived from indanes and tetralines were synthesized. The human carbonic anhydrase isozymes hCA I and hCA II inhibition effects of the synthesized sulfonamides were determined. From these compounds, while N-(5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl)methane sulfonamide showed the most potent inhibitory effect against hCA I (Ki=46 ± 5.4 µM, r(2) =0.978), N-(1,2,3,4-tetrahydronaphthalene-2-yl)methanesulfonamide was found to have the best inhibitory effect against hCA II (Ki=94 ± 7.6 µM, r(2) =0.982).

Novel sulfamides as potential carbonic anhydrase isoenzymes inhibitors.

Sulfamides represent an important class of biologically active compounds. A series of novel sulfamides were synthesized from 1-aminoindanes, 1-aminotetralin, 2-aminoindanes and 2-aminotetralin via the reactions of free amines, benzyl alcohol and chlorosulfonyl isocyanate (CSI) followed by hydrogenolysis of the obtained sulfamoylcarbamates. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the new sulfamides have been investigated. The human (h) isozymes hCA I and hCA II have been investigated in this study by using an esterase assay with 4-nitrophenyl acetate as substrate. The new sulfamides showed inhibition constants in the micro-submicromolar range, with one compound (N-(indane-1-yl)sulfamide) showing a Ki of 0.45µM against hCA I and of 1.07µM against hCA II.

Synthesis, antioxidant, and antiacetylcholinesterase activities of sulfonamide derivatives of dopamine-related compounds.

A series of sulfonamides were synthesized from dopamine derivatives. The reactions of amines with methanesulfonyl chloride followed by O-demethylation with BBr3 afforded phenolic sulfonamides. The antioxidant activities of the synthesized phenolic sulfonamides were investigated by thiocyanate method, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(•+)), 1,1-diphenyl-2-picryl-hydrazyl (DPPH(•)), N,N-dimethyl-p-phenylenediamine (DMPD(•+)), and superoxide anion (O2(•-)) radical scavenging, reducing power, and ferrous ion (Fe(2+)) chelating assays. Sulfonamides 13-16 showed around 75-85% inhibition on linoleic acid peroxidation. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol, and trolox indicated an inhibition of 90.0%, 85.73%, 73.33%, and 85.73% on peroxidation, respectively, in the same system at the same concentration (10 µg/mL). Also, the inhibition effects of the synthesized compounds on acetylcholinesterase (AChE) activity were evaluated. AChE was effectively inhibited by sulfanomides 13-16, with K(i) values in the range of 33.04 ± 4.3 to 131.68 ± 8.8 nM.

Synthesis and antioxidant properties of (3,4-dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone and its derivatives.

(3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone (5) and its two derivatives with bromine were synthesized from reactions such as bromination and demethylation of (3,4-dimethoxyphenyl)(2,3,4-trimethoxyphenyl)methanone (6). The Wolf-Kishner reduction product (9) of 6 and its three derivatives with bromine were obtained. 4-(3,4-Dihydroxybenzyl)benzene-1,2,3-triol and its dibromide derivative (16) were also synthesized from 9 and the corresponding dibromide derivative. The in vitro antioxidant activities of nine new compounds synthesized in these reactions were determined by analyzing the radical scavenging activities of bromophenols for 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picryl-hydrazyl (DPPH), N,N-dimethyl-p-phenylenediamine (DMPD), and the superoxide anion radical (O(2)(·-)) and examining the total reducing power through Fe(3+)-Fe(2+) transformation, FRAP and CUPRAC assays and the ferrous ions (Fe(2+)) chelating activities. Moreover, the results of these activities were compared to those of standard antioxidant compounds such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol, and trolox. The results showed that the synthesized bromophenols had effective antioxidant power. The phenol 5 with two phenolic rings and five phenolic hydroxyl groups was the most potent antioxidant and radical scavenger. In conclusion, the new compounds are promising molecules to be used owing to their potential antioxidant properties.

Caffeic acid phenethyl ester (CAPE): correlation of structure and antioxidant properties.

Caffeic acid phenethyl ester (CAPE), a plant polyphenolic concentrated in honeybee propolis, has been found to be biologically active in a variety of pathways. The aim of this study was to determine the antioxidant activity of CAPE using different methods such as total antioxidant activity by the thiocyanate method, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid radicals, 1,1-diphenyl-2-picryl-hydrazyl free radicals, N,N-dimethyl-p-phenylenediamine dihydrochloride radicals and superoxide anion radicals scavenging activities, reducing power and ferrous ions (Fe(2+)) chelating activities. CAPE showed 97.9% inhibition on lipid peroxidation of linoleic acid emulsion. On the other hand, butylated hydroxyanisole, butylated hydroxytoluene, α-tocopherol and trolox indicated an inhibition of 87.3, 97.6, 75.3 and 90.3% on peroxidation in the same system, respectively.