Two new morphinane alkaloids from Sinomenium acutum.

Two new morphinane alkaloids, 1-hydroxy-10-oxo-sinomenine (1) and 4,5-epoxy-14-hydroxy sinomenine N-oxide (2), have been isolated from the stems of Sinomenium acutum. Their structures were established by various spectral analyses, especially 2D NMR experiments. The structure of 2 was confirmed by single crystal X-ray diffraction. The absolute configurations of 1 and 2 were deduced by comparison of CD spectra with the known alkaloid sinomenine (3). Compound 1 was tested for DPPH inhibition and gave IC(50) of 27.9 µM. Compound 2 was tested for neuroprotective effect and showed significant activity against ß-amyloid(25-35)-induced oxidative injury (*P < 0.05) at 10 µM in PC-12 cells.

Synthesis of various kinds of isoflavones, isoflavanes, and biphenyl-ketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities.

Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10') were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED(50)=12-54 microM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E-I) and their biphenyl-ketone derivatives (10E-H) also showed a high activity (ED(50)=or<50 microM), while all of their corresponding isoflavones (8E-I) were not active at all. The 7-hydroxyisoflavanes having either an additional hydroxyl group at the C5-position (9D) or a methoxy group at the C6-position (9J) presented a high activity (ED(50)=26-32 microM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3'-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10') by metabolism or biotransformation.

Fish skin as a model membrane: structure and characteristics.

OBJECTIVES: Synthetic and cell-based membranes are frequently used during drug formulation development for the assessment of drug availability. However, most of the currently used membranes do not mimic mucosal membranes well, especially the aqueous mucous layer of the membranes. In this study we evaluated catfish (Anarichas lupus L) skin as a model membrane. METHOD: Permeation of hydrocortisone, lidocaine hydrochloride, benzocaine, diethylstilbestrol, naproxen, picric acid and sodium nitrate through skin from a freshly caught catfish was determined in Franz diffusion cells. KEY FINDINGS: Both lipophilic and hydrophilic molecules permeate through catfish skin via hydrated channels or aqueous pores. No correlation was observed between the octanol/water partition coefficient of the permeating molecules and their permeability coefficient through the skin. Permeation through catfish skin was found to be diffusion controlled. CONCLUSIONS: The results suggest that permeation through the fish skin proceeds via a diffusion-controlled process, a process that is similar to drug permeation through the aqueous mucous layer of a mucosal membrane. In addition, the fish skin, with its collagen matrix structure, appears to possess similar properties to the eye sclera.

Abnormal solvent effects on hydrogen atom abstraction. 2. Resolution of the curcumin antioxidant controversy. The role of sequential proton loss electron transfer.

The rates of reaction of 1,1-diphenyl-2-picrylhydrazyl (dpph*) radicals with curcumin (CU, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), dehydrozingerone (DHZ, "half-curcumin"), and isoeugenol (IE) have been measured in methanol and ethanol and in two non-hydroxylic solvents, dioxane and ethyl acetate, which have about the same hydrogen-bond-accepting abilities as the alcohols. The reactions of all three substrates are orders of magnitude faster in the alcohols, but these high rates can be suppressed to values essentially equal to those in the two non-hydroxylic solvents by the addition of acetic acid. The fast reactions in alcohols are attributed to the reaction of dpph* with the CU, DHZ, and IE anions (see J. Org. Chem. 2003, 68, 3433), a process which we herein name sequential proton loss electron transfer (SPLET). The most acidic group in CU is the central keto-enol moiety. Following CU's ionization to a monoanion, ET from the [-(O)CCHC(O)-](-) moiety to dpph* yields the neutral [-(O)CCHC(O)-]* radical moiety which will be strongly electron withdrawing. Consequently, a phenolic proton is quickly lost into the alcohol solvent. The phenoxide anion so formed undergoes charge migration to produce a neutral phenoxyl radical and the keto-enol anion, i.e., the same product as would be formed by a hydrogen atom transfer (HAT) from the phenolic group of the CU monoanion. The SPLET process cannot occur in a nonionizing solvent. The controversy as to whether the central keto-enol moiety or the peripheral phenolic hydroxyl groups of CU are involved in its radical trapping (antioxidant) activity is therefore resolved. In ionizing solvents, electron-deficient radicals will react with CU by a rapid SPLET process but in nonionizing solvents, or in the presence of acid, they will react by a slower HAT process involving one of the phenolic hydroxyl groups.

Hyperjovinols A and B: Two new phloroglucinol derivatives from Hypericum jovis with antioxidant activity in cell cultures.

Two new and four known phloroglucinol derivatives were isolated from the dichloromethane extract of the Greek endemic plant Hypericum jovis. Their antioxidant activity was evaluated in vitro with the DPPH assay and in cell cultures using the DCFH-DA assay. All six compounds demonstrated significant antioxidant activity, while two of them possessed activity at a cellular level comparable to Trolox, protecting against ROS.

Acute toxicity, distribution, and metabolism of 2,4,6-trinitrophenol (picric acid) in Fischer 344 rats.

Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military, and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4 h with a gut absorption coefficient (ka) of 0.069 h-1. Twenty-four hours following oral administration of [14C]picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver, lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity. Tissue/blood ratios were essentially maintained over a 48-h postadministration period. Binding (in vitro) of [14C]picric acid to plasma proteins (whole blood preparations) demonstrated both high- and low-affinity binding sites, with dissociation constants of 3.18 x 10(-6) and 2.85 x 10(-4) M, respectively. The findings of this investigation provide information on the acute toxicity, metabolism, and distribution of picric acid, which can be used in risk assessment analyses and in the design of subchronic and chronic toxicity tests.

A quimica e a cinética da reaçäo de Jaffé / Chemistry and Kinetics from Jaffé reaction

A reaçäo de Jaffé modificada é largamente empregada na rotina laboratorial para dosagem de creatinina. Entretanto, encontra-se dificuldades na identificaçäo do real quimismo e sua cinética. Nesta publicaçäo, propomo-nos a elucidaçäo do mecanismo com correspondente análise cinética