Platelet aggregation inhibitors from Populus sieboldii Miquel.

The water extract of Populus sieboldii Miquel (Salicaceae) inhibited arachidonic acid-induced platelet aggregation. Pyrocatechol and salicyl alcohol were isolated as active constituents. Pyrocatechol showed an inhibitory effect on platelet aggregation induced by arachidonic acid with IC100 value of 4 microM, which was 25 times more potent than aspirin.     

Free radical oxidation of dihydric phenols with diphenylpicrylhydrazyl

A spectrophotometric study has been made of the reactions between the free radical 2,2-dipheny1-1-picrylhydrazyl (DPPH) and the three dihydric phenols. It has been shown that water affects the rate of all three reactions and the stoichiometry of the DPPH-catechol (pyrocatechol) reaction. Because of the differences in the rate of oxidation in absolute ethanol, it is possible to determine selectively either hydroquinone or catechol in the presence of resorcinol.     

Synthesis and platelet aggregation inhibitory activity of diphenylazole derivatives. I. Thiazole and imidazole derivatives

Diphenylimidazole and diphenylthiazole derivatives were synthesized and tested as inhibitors of platelet aggregation in in vitro experiments with the rabbit. Diphenylthiazole derivatives (10) were more potent than diphenylimidazole derivatives (4) in inhibiting arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. Two diphenylimidazole and eight diphenylthiazole derivatives were evaluated for ex vivo arachidonic acid and collagen-induced platelet aggregation inhibitory activity using guinea pigs. In these compounds, 4,5-bis(4-methoxyphenyl)-2-(1,5-dimethyl-2-pyrrolyl)thiazole (10n) showed strong activity in vitro and ex vivo. The ex vivo activity of 10n was 200 times stronger than that of aspirin. The mechanism of the activity of 10n was the inhibition of cyclo-oxygenase.     

The inhibitory effect of bis[2-[(E)-2-octenoylamino]ethyl] disulfide on the cyclooxygenase pathway

Bis[2-[(E)-2-octenoylamino]ethyl] disulfide (compd. I-3) inhibited collagen- and arachidonic acid-induced rat platelet aggregation, although not adenosine 5'-diphosphate (ADP)-induced rat platelet aggregation. Based on these results, we then investigated the inhibitory effect of compd. I-3 on thromboxane B2 formation from arachidonic acid in rat platelets, and prostaglandin I2 formation in rat aortae. Compound I-3 inhibited both thromboxane B2 and prostaglandin I2 formation, suggesting that it has an inhibitory effect on cyclooxygenase. The inhibitory effect of compd. I-3 was confirmed in experiments using a crude preparation of sheep seminal vesicle microsomal prostaglandin synthetase. These findings suggested that compd. I-3 has an inhibitory effect on cyclooxygenase activity, like nonsteroidal anti-inflammatory drugs.     

Thin-layer chromatography of dihydric phenols

Summary Phenol, resorcinol, catechol, and hydroquinone were separated on thin layers of silica gel impregnated with silver nitrate. The incorporation of silver nitrate in the adsorbent layer results in the oxidation of ortho and para dihydric phenols to the corresponding benzoquinones, meta dihydric phenols are not changed, hence the separation of the dihydric isomers is possible.

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Zusammenfassung Phenol, o-, m- und p-Dihydroxybenzole werden auf mit Silbernitrat imprägnierten Kieselgel-Dünnschichtplatten aufgetrennt. Diese Trennung wird dadurch möglich, daß in Anwesenheit von Silbernitrat o- und p-Dihydroxybenzole zu den entsprechenden Benzochinonen oxydiert werden, bei m-Dihydroxybenzol diese Oxydation jedoch nicht eintritt.

     

Preparation and antiplatelet activity of glycidic acid derivatives

Arylalkanoic acid derivatives exhibit a variety of biological effects. In the current publication some of new glycidic acid derivatives were prepared via the Darzens condensation. The synthetic approach, analytical and spectroscopic data of all newly synthesized compounds are presented. The prepared compounds were evaluated as potential inhibitors of arachidonic acid-induced platelet aggregation and their activity was compared with that of acetylsalicylic acid as the standard. (±)-Ethyl 3-{4-[(4-methoxyphenyl)sulfanyl]phenyl}-3-methyl-cis-oxirane-2-carboxylate (IC₅₀ = 0.07 mmol L⁻¹) and (±)-3-{4-[(4-methoxyphenyl)sulfanyl]phenyl}-3-methyl-cis-oxirane-2-carboxylic acid (IC₅₀ = 0.06 mmol L⁻¹) showed the highest antiplatelet activity against arachidonic acid-induced platelet aggregation comparable with the standard. Structure-activity relationships between the chemical structure, lipophilicity, and the antiplatelet activity of the evaluated compounds are discussed.     

奥拉西坦衍生物的设计、合成及抗血小板聚集活性研究

本文采用拼合策略,设计、合成了7个新型奥拉西坦衍生物。其中,化合物4a～4f由奥拉西坦与苯丙烯酸片段拼合得到; 4g则由奥拉西坦、吲哚布芬拼合得到。采用Bron比浊法测定目标化合物对花生四烯酸及二磷酸腺苷诱导的血小板聚集的抑制活性。结果表明,该系列化合物具有一定的抗血小板聚集活性,其中化合物4f的抗血小板聚集活性与阳性对照吲哚布芬相当。     

Inhibitory effects of 2'-hydroxychalcones on rat lens aldose reductase and rat platelet aggregation

Inhibitory effects of synthetic 2'-hydroxychalcone derivatives on rat lens aldose reductase (RLAR) and on platelet aggregation were investigated for the prevention or the treatment of chronic diabetic complications. 5'-chloro-4,2'-dihydroxychalcone (8) and 5'-chloro-3,2'-dihydroxychalcone (27) exhibited a potent inhibitory effect on rat platelet aggregation induced by ADP (IC50=0.10 and 0.06 mg/ml, respectively) and collagen (IC50=44 and 16 microg/ml, respectively) but showed relatively weak inhibitory activities on RLAR.     

Laser Desorption Ionization of Arylene Phenylphosphonites Formed by Condensation of Dihydric Phenols with Phenylphosphonous Bis(diethylamide)

Step high-temperature condensation of dihydric phenols [1,4-dihydroxybenzene, 4,4′-dihydroxybiphenyl, and 2,2′-bis(4-hydroxyphenyl)propane] with phenylphosphonous bis(diethylamide) is carried out. The molecular weight, composition, and structure of the resulting oligomeric arylene phenylphosphonites were assessed by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The widest mass range was observed in the mass spectrum of 4,4′-dihydroxybiphenyl, which corresponds to an oligomer having about 30 elementary units. The obtained data agree with the the molecular weight measured by high-speed sedimentation. The reactions of phenylphosphonous bis(diethylamide) with dihydric phenols give both acyclic and cyclic arylene phenylphosphonites.     

A sensitive and selective spectrophotometric estimation of catechol derivatives in pharmaceutical preparations

A sensitive and simple spectrophotometric method for the estimation of catechol and its derivatives like dopamine hydrochloride (DPH), levodopa (LDP), methyldopa (MDP) and adrenaline hydrochloride (ADH) in both pure form and in pharmaceutical formulation, is described. The method is based on the interaction of diazotised sulphanilamide (DSA) with catechol derivatives in the presence of molybdate ions in acidic medium. Absorbance of the resulting red coloured product is measured at 490 nm for pyrocatechol (PCL) and at 500 nm for other catechol derivatives. The colour reaction is stable for 24–30 h. Under optimal conditions, Beer's Law range for pyrocatechol was found to be between 0.04 and 2.4 (R.S.D.=0.78%), for DPH was 0.02–2.8 (R.S.D.=0.98%) for LDP was 0.1–2.8 (R.S.D.=1.21%) for MDP was 0.5–7 (R.S.D.=1.41%) and for ADH was 0.5–7 (R.S.D.=1.58%). The method is highly reproducible and specific for these selected catechol derivatives. The common excipients used as additives do not interfere in the proposed method. Analytical data for the determination of the pure compound is presented together with the application of the proposed method to the analysis of some pharmaceutical formulations. The results compare favourably with those of official and reported methods.     

A semiempirical study on inhibition of catechol O-methyltransferase by substituted catechols

Catechol and endogenous catechol derivatives are readily methylated by catechol O-methyltransferase (COMT). In contrast, many catechol derivatives possessing electronegative substituents are potent COMT inhibitors. The X-ray structure of the active site of COMT suggests that the methylation involves a lysine as a general base. The lysine can activate one of the catecholic hydroxyl groups for a nucleophilic attack on the active methyl group of the coenzyme S-adenosyl-l-methionine (AdoMet). We studied the effect of dinitrosubstitution of the catecholic ring at the semiempirical PM3 level on the methylation reaction catalysed by COMT. The electronegative nitro groups make the ionized catechol hydroxyls less nucleophilic than the corresponding hydroxyl groups of the non-substituted catechol. As a consequence, dinitrocatechol is not methylated but is instead a potent COMT inhibitor. The implications of this mechanism to the design of COMT inhibitors are discussed.     

Anti-Platelet Aggregation and Anti-Cyclooxygenase Activities for a Range of Coffee Extracts (Coffea arabica)

Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total phenolic contents (TPC) and biological activities. Inflammation and increases of platelet activation and aggregation can lead to thrombosis. We focused on determining the chemical composition, antioxidant activity and inhibitory effects on agonist-induced platelet aggregation and cyclooxygenase (COX) of coffee beverages in relation to their preparation method. We prepared instant coffee and brewed coffee beverages using drip, espresso, and boiling techniques. Coffee extracts were assayed for their CF and CGA contents using HPLC, TPC using colorimetry, platelet aggregation with an aggregometer, and COX activity using ELISA. The findings have shown all coffee extracts, except the decaffeinated types, contained nearly equal amounts of CF, CGA, and TPC. Inhibitory effects of coffee extracts on platelet aggregation differed depending on the activation pathways induced by different agonists. All espresso, drip and boiled coffee extracts caused dose dependent inhibition of platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid (ARA). The most marked inhibition was seen at low doses of collagen or ARA. Espresso and drip extracts inhibited collagen-induced platelet aggregation more than purified caffeine or CGA. Espresso, boiled and drip coffee extracts were also a more potent inhibitors of COX-1 and COX-2 than purified caffeine or CGA. We conclude that inhibition of platelet aggregation and COX-1 and COX-2 may contribute to anti-platelet and anti-inflammatory effects of espresso and drip coffee extracts.     

Reactions of synthetic phenolic antioxidants with electrogenerated titrants and their analytical applications

Synthetic phenolic compounds (pyrogallol, catechol, hydroquinone, and their derivatives bearing heterocyclic fragments) react with electrogenerated titrants, halogens, and ferricyanide(III) ions. Stoichiometric coefficients of reactions are found. It is shown that the use of ferricyanide(III) ions as a titrant and a one-electron oxidant for the determination of this class of antioxidants offers advantages in comparison with titrants-halogens. The found amounts of pyrogallol, pyrocatechol, and hydroquinone derivatives in model solutions with the RSD 1–5% are fractions of milligrams. It is found that, in the series of the studied synthetic phenolic compounds, pyrocatechol derivatives possess the maximum antioxidant capacity (AOC).     

Quantitative structure-activity relationship of catechol derivatives inhibiting 5-lipoxygenase.

Various catechol derivatives (beta-substituted 3,4-dihydroxystyrenes, 1-substituted 3,4-dihydroxybenzenes, and 6-substituted 2,3-dihydroxynaphthalenes) were synthesized and their inhibition of 5-lipoxygenase was assayed. Their structure-activity relationships were examined quantitatively with substituent and structural parameters and regression analysis. The variations in the inhibitory activity were explained in bilinear hydrophobic parameter (log P) terms, and steric (molecular thickness) and electronic (proton nuclear magnetic resonance (1H-NMR) chemical shift of the proton adjacent to the catechol group) parameter terms. The hydrophobicity of the inhibitor molecule was important, and the optimum value of logP was about 4.3-4.6, beyond which inhibition did not increase further. A lower electron density of the aromatic ring containing the catechol group and the greater thickness of the lipophilic side chains were unfavorable to the activity. The results added a physicochemical basis for the selection of candidate compounds for developmental studies.     

Reaction of Sterically Congested Phenols and Quinones with Organic Radicals

In the course of radiation-induced free-radical transformations of hexane and ethanol, pyrocatechol and hydroquinone derivatives, as well as their respective quinones, are more effective than phenol and resorcinol derivatives in controlling reactions that involve alkyl and hydroxyalkyl radicals. The opposite result takes place in the inhibition by phenols of hexane oxidation in which the key role belongs to the peroxyl radicals generated from the starting compounds.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 4, 2005, pp. 632–635.Original Russian Text Copyright © 2005 by Edimecheva, Ostrovskaya, Polozov, Shadyro.     

Synthesis of selenium-containing derivatives of <Emphasis Type="Italic">para</Emphasis>-bromopropyl-substituted phenols

The dynamics of changes in the composition of the reaction mixture during the reaction of Na₂SeSO₃ and bromopropyl-substituted phenol in 50% aqueous ethanol and under the conditions of decreasing EtOH concentration in the reaction medium was studied. Convenient methods for the synthesis of 3-(4-hydroxyaryl)propyl selenosulfates and the corresponding diselenides were proposed. Symmetrical and unsymmetrical selenides (derivatives of alkylated phenols and pyrocatechol) were synthesized.     

Microdetermination of phenols, carboxylic acids and phenolic acids by potentiometric and visual titrations in dimethylformamide

Potentiometric titration of phenols with sodium methoxide in dimethylformamide, with a glass-calomel electrode system, is limited to monohydric phenols substituted with electron-attracting groups and dihydric phenols in which the two -OH groups are substituted in isolated benzene rings. Brilliant Orange has proved to be a suitable indicator in the titration of all types of mono- and dihydric phenols. Titan Yellow is recommended as indicator for the titration of carboxylic acids. Simultaneous visual titration of -OH and -COOH groups is also described. A detailed study with 62 structurally different compounds covering the various groups is reported, and a suitable procedure for the microdetermination of each class of these compounds with an error of +/- 0.2% absolute or less is presented.     

Empirical procedure for the calculation of ionization constants of organic compounds in water from their molecular volume

An empirical procedure was used to calculate 278 ionization constants of 271 organic compounds, including phenols, NH acids, benzoic acid derivatives, and mono- and dihydric carboxylic acids, in water. The examined compounds were divided into 11 structural groups. The ionization constants for compounds belonging to a single group were calculated from constant empirical coefficients, molecular volumes, and formulas with an average error of less than 3.5%, the maximal error not exceeding 9.9%.     

Studies on antiinflammatory agents. I. Synthesis and pharmacological properties of 2'-phenoxymethanesulfonanilide derivatives.

Various 2'-phenoxymethanesulfonanilide derivatives were synthesized and evaluated for antiinflammatory and analgesic activities. Some compounds bearing an electron-attracting substituent at the 4'-position strongly inhibited adjuvant-induced arthritis in rats and acetic acid-induced writhing syndrome in mice without causing gastro-intestinal irritation. Among them, 4'-cyano-(FK867) and 4'-acetyl-(FK3311) 2'-(2,4-difluorophenoxy)methanesulfonanilides were selected as the candidates for further development.     

Advances in the studies of bisphosphorylated dihydric phenols

The data on the synthesis, structure, and chemical properties of bisphosphorylated dihydric phenols are summarized. All the currently known methods for the synthesis of the systems in question are shown. Specific features of their structure, chemical and complexation properties, as well as areas of application of these compounds were analyzed.