Trihydroxy Compounds Research Articles

Rice peroxygenase catalyzes lipoxygenase-dependent regiospecific epoxidation of lipid peroxides in the response to abiotic stressors

The peroxygenase pathway plays pivotal roles in plant responses to oxidative stress and other environmental stressors. Analysis of a network of co-expressed stress-regulated rice genes demonstrated that expression of OsPXG9 is negatively correlated with expression of genes involved in jasmonic acid biosynthesis. DNA sequence analysis and structure/function studies reveal that OsPXG9 is a caleosin-like peroxygenase with amphipathic α-helices that localizes to lipid droplets in rice cells. Enzymatic studies demonstrate that 12-epoxidation is slightly more favorable with 9(S)-hydroperoxyoctadecatrienoic acid than with 9(S)-hydroperoxyoctadecadienoic acid as substrate. The products of 12-epoxidation are labile, and the epoxide ring is hydrolytically cleaved into corresponding trihydroxy compounds. On the other hand, OsPXG9 catalyzed 15-epoxidation of 13(S)-hydroperoxyoctadecatrienoic acid generates a relatively stable epoxide product. Therefore, the regiospecific 12- or 15-epoxidation catalyzed by OsPXG9 strongly depends on activation of the 9- or 13- peroxygenase reaction pathways, with their respective preferred substrates. The relative abundance of products in the 9-PXG and 13-PXG pathways suggest that the 12-epoxidation involves intramolecular oxygen transfer while the 15-epoxidation can proceed via intramolecular or intermolecular oxygen transfer. Expression of OsPXG9 is up-regulated by abiotic stimuli such as drought and salt stress, but it is down-regulated by biotic stimuli such as flagellin 22 and salicylic acid. The results suggest that the primary function of OsPXG9 is to modulate the level of lipid peroxides to facilitate effective defense responses to abiotic and biotic stressors.

Rational design, synthesis and activities of hydroxylated chalcones as highly potent dual functional agents against Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the extracellular amyloid plaques in the brain. Recent studies have shown that ferroptosis, a recently identified cell death pathway associated with the accumulation of lipid hydroperoxides, is closely related to the occurrence and exacerbation of AD. The application of ferroptosis inhibitors can alleviate the development of AD in both cellular and animal models. Herein, a series of dual-functional hydroxylated chalcone derivatives by integrating the heterocyclic dimethylaminopyrimidine in the core structure were designed and synthesized beyond our previous research to optimize their inhibition activities towards Aβ protein aggregation and ferroptosis simultaneously. The inhibitory ability of the novel synthesized chalcone derivatives were greatly improved. The results indicated that the introduction of the dimethylaminopyrimidine structure provided improved effect on Aβ protein aggregation inhibitory activity in both solution and cellular models. Trihydroxy chalcone derivative A-N-5 provided the best inhibition activities against Aβ protein aggregation in cellular models. The trihydroxy compound A-N-5 did not show cytotoxicity at the concentration lower than 100 µM (with IC50 > 1 mM), but had a significant effect on promoting cell proliferation. Results indicated that compound A-N-5 could potentially promote neuronal cell growth in the damaged brain tissue. The compound could also inhibit ferroptosis induced by RSL or erastin and reduce the lipid peroxidation levels induced by Aβ1-42 protein aggregation. Molecular docking was also conducted to explain the better inhibitory effect of novel compounds to inhibit Aβ protein aggregation compared to the previous designed molecules without incorporation of the dimethylaminopyrimidine. In summary, the trihydroxy compound A-N-5 showed the best inhibition activities against Aβ aggregation as well as ferroptosis with low cytotoxicity as a promising molecular skeleton candidate for further development of lead compound for in vivo test to treat AD.

Antifungal toxicity of linear geranylphenol. Influence of oxigenate substituents

Twenty four linear geranylphenols were evaluated for their antifungal properties against ATCC and clinical isolates of Candida albicans and Cryptococcus neoformans. For the analysis of their antifungal behavior the compounds were grouped into two series: (i) compounds with only one geranyl substituent on the benzene ring and (ii) compounds with two geranyl moieties on the benzene ring. Results showed that compounds of series (i) present better antifungal activities than those of series (ii). In addition, within group (i) all compounds showed better activities against C. neoformans than against C. albicans which can be easily verified by comparing MIC100 or MIC50 of each compound against both fungi. Di- (10 and 11) and tri-hydroxy (3 and 4) compounds showed significant anti-cryptoccocal activity, being 3, 10 and 11 highly active with MIC100 or MIC50 = 3.9 μg/mL similar to the standard drug amphotericin B. Moreover, when evaluating the toxicity of compounds 6, 10 and 11 on the HDF cell line (human dermal fibroblasts), results were obtained with IC50 values > 100 μM, considered as non-toxic for the cell. This indicates that the toxicity of the analyzed compounds is selective towards fungi, which makes them a very attractive family for the development of future drugs.

Evaluating anti-Toxoplasma gondii activity of new serie of phenylsemicarbazone and phenylthiosemicarbazones in vitro

While Toxoplasma gondii is able to infect and replicate within all eukaryotic cells, tachyzoites are the infective form of T. gondii that invades all eukaryotic cells leading to tissue rupture, the main features of toxoplasmosis. The present study evaluates the activity of (benzaldehyde)-4-phenyl-3-thiosemicarbazone and (benzaldehyde)-(4 or 1)-phenylsemicarbazone against intracellular T. gondii. The nine new compounds were incubated in infected Vero cells at concentrations of 0.01, 0.1, 0.5, and 1.0 mM and evaluated for three main effects: cytotoxicity, infection, and number of intracellular parasites. The cytotoxicity test showed a pattern by analyzing the substituent arylhydrazone, where trihydroxy Compounds 4–9 were cytotoxic at concentrations of 0.5 and 1.0 mM. The results highlight Compound 8, which reduced the number of intracellular parasites by 82 % in a concentration of 0.01 mM and showed a LD50 of 0.3 mM in cell culture. These different biological actions are due to changes in the molecular structure and type of radical present in each compound. All compounds tested were more efficient than the control drug sulfadizine.

Caroteniod 5,6-, 5,8- and 3,6-epoxides

The isolation, semisynthesis and structure elucidation of carotenoid 5,6-, 5,8- and 3,6-epoxides as well as their derivatives are discussed in detail. This review gives a brief summary of the plausible biosynthetic transformations of the 5,6- epoxy-β-ring. A wide variety of carotenoid end-groups can be obtained from 5,6-epoxy carotenoids. In order to get information on the enzyme activities and regulation of the biosynthetic pathway of carotenoids some of the intermediate steps of these transformations were investigated (e.g. formation of allenic, κ- and γ-end-groups as well as ring opening reactions). The ring opening of the 3-hydroxy-5,6-epoxy end group, resulting in the formation of 3,5,6- trihydroxy compounds, was studied in detail in order to obtain evidence for the proposed reaction mechanisms of the two different biosynthetic routes (acid or enzyme catalysis) which also explain the configurations at the C(5) and C(6) atoms.

ChemInform Abstract: Organophosphorus Compounds. Part 18. The Reaction of Lawesson′s Reagent with Trihydroxy Compounds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The reaction of Lawesson's reagent with trihydroxy compounds

The reaction of Lawesson's reagent with trihydroxy compounds

The reaction of Lawesson's reagent with trihydroxy compounds

Lawesson's reagent (1a) reacts with pyrogallol (2) to give 1,3,2-benzodioxaphospholane-2-sulfide (3) and with 1,8,9-trihydroxyanthracene to give 13. The structures of the products have been established either chemically, using methanolysis and methylation, or spectroscopically. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 25–30, 1999

The reaction of Lawesson's reagent with trihydroxy compounds

The reaction of Lawesson's reagent with trihydroxy compounds

On the cytotoxity of oxidized phytosterols isolated from photoautotrophic cell cultures of Chenopodium rubrum tested on meal-worms Tenebrio molitor

Cell injury—as evoked by oxidative stress, insect attack or ageing—causes lipid peroxidation of polyunsaturated acids, e.g. linoleic acid. Hydroperoxides (LOOH) so produced transform fatty acids, terpenes and sterols to epoxides. We describe a bioassay to determine the cytotoxity of sterol oxidation products by measuring the mortality of meal-worms ( Tenebrio molitor) after injection of diluted test compounds. LOOH was tested in concentrations from 10 −5 M up to 10 −2 M and developed recognizable mortality (25%, 10 −2M, 23 hr). A direct relation between activity and concentration was observed. 5,6-Epoxides of phytosterols and derived 3,5,6-trihydroxysteranes have been isolated from Chenopodium rubrum cell cultures. Using 5,6-epoxycholesterol and 3,5,6-trihydroxycholestane as standards of known bioactivity, the toxicity of epoxides of sitosterol and stigmasterol, as well as the trihydroxy compounds thereof, was checked. The phytosterol derivatives are by a factor of five less active than the corresponding cholesterol oxidation products. 5,6-Epoxides and 5,6-chlorohydrins showed half of the activity of the corresponding 3,5,6-trihydroxyphytosterols. These developed highest cytotoxity (40% mortality in 5 × 10 −3 M solution after 23 hr). The activity of 5,6α-and 5,6β-epoxides was found to be equal. Metabolism and proposed biological function of oxidized phytosterols is discussed.

Heavily-substituted calix[4]arenes derived from p-Cyanomethylcalix[4]arene

p-Cyanomethylcalix[4]arene ( 1b) can be converted in good yield to compounds containing twelve arylmethyl groups, four attached to the phenolic oxygens and eight to the carbons α to the CN groups. Depending upon the reaction protocol the products can be obtained either in the 1,3-alternate ( 3) or cone ( 4) conformation. Complete debenzylation or selective debenzylation (to monohydroxy and trihydroxy compounds) can be effected with AlCl 3 and Me 3SiBr, respectively.

Natural antioxidants from low-pungency mustard flour

The ethanolic extracts of low-pungency mustard flour were separated on a Sephadex LH-20 column. Three major fractions were separated according to the UV absorbance readings at 280 nm. Antioxidant activity of these fractions was evaluated in a β-carotene-linoleate model system. Fraction I was most effective and showed absorbance readings similar to those of sinapic acid, p-hydroxybenzoic acid and trihydroxy phenolic compounds such as flavones or flavanones. Fraction II exhibited moderate antioxidant activity and showed the possible presence of phenolic acids and trihydroxy compounds. Fraction III was least effective and did not contain any trihydroxy compounds as indicated by a thin layer chromatography spray method.

Enzymatic monoacylation of trihydroxy compounds

Using phenylboronic acid as solubilizing agent in nonpolar solvents the lipase-catalyzed monoacylation of glycerol with uncommon fatty acids like (S)-17-hydroxy stearic acid was successful. 1-monostearoyl-5,6-dihydroxy hexane was prepared by an alternative classical route.

Metabolism of dibenzo-p-dioxin by Sphingomonas sp. strain RW1.

In the course of our screening for dibenzo-p-dioxin-utilizing bacteria, a Sphingomonas sp. strain was isolated from enrichment cultures inoculated with water samples from the river Elbe. The isolate grew with both the biaryl ethers dibenzo-p-dioxin and dibenzofuran (DF) as the sole sources of carbon and energy, showing doubling times of about 8 and 5 h, respectively. Biodegradation of the two aromatic compounds initially proceeded after an oxygenolytic attack at the angular position adjacent to the ether bridge, producing 2,2',3-trihydroxydiphenyl ether or 2,2',3-trihydroxybiphenyl from the initially formed dihydrodiols, which represent extremely unstable hemiacetals. Results obtained from determinations of enzyme activities and oxygen consumption suggest meta cleavage of the trihydroxy compounds. During dibenzofuran degradation, hydrolysis of 2-hydroxy-6-oxo-6-(2-hydroxyphenyl)-hexa-2,4-dienoate yielded salicylate, which was branched into the catechol meta cleavage pathway and the gentisate pathway. Catechol obtained from the product of meta ring fission of 2,2',3-trihydroxydiphenyl ether was both ortho and meta cleaved by Sphingomonas sp. strain RW1 when this organism was grown with dibenzo-p-dioxin.

In vitro metabolism of cannabidiol in the rabbit: Identification of seventeen new metabolites including thirteen dihydroxylated in the isopropenyl chain

The metabolism of cannabidiol (CBD) was studied in liver microsomes from the female New Zealand white rabbit. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and examined as trimethylsilyl (TMS), methyl ester/TMS and (2H9)TMS derivatives by gas chromatography/mass spectrometry. Thirty-nine metabolites, mainly mono-, di- and tri-hydroxy compounds, were identified; 17 of these have not been reported before. New metabolites included 8,9-dihydroxy-8,9-dihydro-CBD (two isomers) and seven monohydroxy derivatives of each of these two compounds. The mass spectra of the TMS derivatives of metabolites not hydroxylated in the isopropenyl group were generally dominated by the ion produced by retro-Diels-Alder cleavage of the terpene ring. Other structurally informative ions included the tropylium ion and fragments diagnostic of hydroxylation at C-1", C-2", C-3", C-4" and C-7. The spectra of the TMS derivatives of metabolites hydroxylated in the isopropenyl group were generally dominated by the ion at m/z 143. This involved loss of CH2OTMS and a retro-Diels-Alder fragmentation analogous to that seen in the other metabolites, but with charge retention by the other (smaller) fragment. Other, related fragment ions also characterized these metabolites.

Metabolism of 3α, 7α-dihydrexy-7β-methyl-5β-cholanoic acid and 3α,7β-dihydroxy-7α-methyi-5β-cholanoic acid in hamsters

The metabolic fate of the bile add analogs, 3α,7α-dihydroxy-7β-methyl-5β-cholanoic acid and 3α,7β-dihydroxy-7α-methyl-5β-cholanoic acid, was investigated and compared with that of chenodeoxycholic acid in hamsters. Both bile acid analogs were absorbed rapidly from the intestine and excreted into bile at similar to that of chenodeoxycholic acid. In the strain of hamster studied, the biliary bile were conjugated with both glycine and taurine. After continuous intravenous infusion, chenodeoxycholic acid the analogs became the major bile acid constituents in bile. After oral administration of a single dose of these compounds, fecal analysis revealed the existence of unchanged material (25–35%) as well as considerable amounts of metabolites (65–75%). The major metabolites excreted into feces were more polar than the starting material and were tentatively identified as trifaydroxy-7-methyl compounds by radioactive thin-layer chromatography. However, monohydroxy compounds were also found in the fecal extracts. These results show that chenodeoxycholic acid and ursodeoxycholic acid with a methyl group at the 7-position are resistant to bacterial 7-dehydroxylation than the normally occurring bile acids and that a certain proportion of these analogs is hydroxylated to give the corespondiag trihydroxy compound(s), In a control experiment, about 5% of administered chenodeoxychoulic acid was metabolized to a trihydroxy feile acid, but most of the compound (95%) was transformed into lithocholic acid.

Structure-activity studies on open-chain analogues of nucleosides: Inhibition of S-adenosyl-L-homocysteine hydrolase and antiviral activity 2. Acid open-chain analogues

Over 50 ω-carboxyalkyl derivatives of adenine and other purine bases were examined for their inhibitory effects on rat liver S-adenosyl-L-homocysteine hydrolase and their antiviral activity. To be an inhibitor of SAH-hydrolase the analogue must contain an adenine base substituted at the position 9 by an ω-carboxyalkyl (C3-C5) chain bearing at least one hydroxyl function. The absolute configuration at the side-chain is decisive for the dihydroxy and trihydroxy compounds, but less important for the monohydroxyalkanoic acids. D-Eritadenine (1a) and 3-(adenin-9-yl)-2-hydroxypropanoic acids (12a) are the most potent SAH-hydrolase inhibitors and the only compounds possessing an antiviral activity (against vesicular stomatitis, parainfluenza type 3, reovirus type 1, and vaccinia virus). All these compounds effect a rapid irreversible inactivation of SAH-hydrolase. The esters of 1a and 12a exhibit little, if any inhibitory activity toward the enzyme; they are, however, much more potent antiviral agents than the parent compounds 1a and 12a, most probably acting as prodrugs of the latter. 2-Amino-D-eritadenine, (2R,3R)-5-(adenin-9-yl)-2,3-dihydroxypentanoic acid, 9-(dicarboxymethyl)adenine, 4-(adenin-9-yl)-2-hydroxybutanoic acid, 3-(8-bromoadenin-9-yl)-2-hydroxypropanoic acid and O-carboxymethyl derivatives of 9-(2,3-dihydroxypropyl)- and 9-(2,3,4-trihydroxybutyl)adenine are described as novel compounds.

Identification of antimicrobial compounds in heated neutral glucose and fructose solutions

The antimicrobial activity occurring in heated neutral glucose and fructose solutions was shown to result from phenolic di- or tri-hydroxy compounds. Twelve such compounds were identified in glucose solutions heated for 120 minutes at 120 °C. The antimicrobial spectra of these compounds were also investigated.

The isolation and structure of tricyclosolidagolactone, a new diterpene from solidago altissima l.

Tricyclosolidagolactone has been isolated from the leaves of Solidago altissima L., and its structure also been elucidated on the basis of its spectral data coupled with an X-ray crystallographic analysis of the corresponding trihydroxy compound produced on LiAlH 4 reduction.

Gas chromatography-mass spectrometric analysis of 3-methyl-cholanthrene metabolism in vivo.

Metabolites of 3-methylcholanthrene in tissues and excreta of rats and mice were extracted, directly or after removal from conjugation, with ethanol or ethyl acetate, purified by Sephadex LH-20 column chromatography, and examined by gas chromatography-mass spectrometric analysis. Data from the present experiments showed that the extracts after chromatographic purification were contaminated with some tissue-derived sterols such as cholesterol. As compounds related to 3-methylcholanthrene, a dehydro compound, 1- and 2-hydroxy compounds, 11-phenol and two other phenols were identified in the extracts. Some Ketones and cis-1,2-dihydroxy compounds were also detected on occasion. Some trihydroxy compounds were suggested. This is of interest because the trihydroxylated metabolites have been pointed out as precursors of ultimate carcinogen of MC recently. The high sensitivity of the lung to MC carcinogenesis was not interpreted only by specific distribution in tissue of metabolites of the hydrocarbon.