New dihydrophenanthrene and phenyldihydroisocoumarin constituents of Trema orientalis.

In the course of the chemical investigation of extracts of the trunk bark and root bark of Trema orientalis, three new compounds were isolated, namely, (9S*,10S*)-3-[7-(3,10-dihydroxy-9-hydroxymethyl-2,5-dimethoxy)-9,10-dihydrophenanthrenyl]propenal (1), (9S*,10S*)-3-[7-(5-O-beta-glucopyranosyl-10-hydroxy-9-hydroxymethyl-2,6-dimethoxy)-9,10-dihydrophenanthrenyl]propenal (2), and (3R*,3aR*,4R*,5S*)-6-O-alpha-arabinopyranosyl-8-hydroxy-3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)-5-(3,5-dihydroxyphenyl)-3,3a-dihydrocyclopenta[1,2,3-de]isobenzopyran-1-one (3, orientoside A). The structures of 1-3 were determined by spectral methods.

Synthesis and alpha-adrenergic binding ligand affinities of 2-iminoimidazolidine derivatives.

In order to obtain possible veinotonic drugs acting through alpha2 receptor activation, we prepared clonidine analogues in which the 2-imino-imidazolidine was attached to various aliphatic or aromatic heterocycles. Among them, the two benzopyranic derivatives 16 and 22 exhibited interesting affinities (19 and 95 nM respectively on [3H]rauwolscine binding, compared to 35 nM for clonidine). Their affinity for alpha1 receptors was found to be much lower: 7570 and 5030 nM for 16 and 22 respectively, suggesting 16 to be 400 times more selective for alpha2 than for alpha1-adrenoceptors.

Synthesis, activity, and molecular modeling of new 2, 4-dioxo-5-(naphthylmethylene)-3-thiazolidineacetic acids and 2-thioxo analogues as potent aldose reductase inhibitors.

A series of 2,4-dioxo-5-(2-naphthylmethylene)-3-thiazolidineacetic acids and 2-thioxo analogues have been prepared as aldose reductase inhibitors. In vitro inhibitory activities of bovine lens aldose reductase were determined by a conventional method. 1-Naphthyl-substituted derivatives of the 2-thioxo series were the more potent inhibitors (IC50 congruent with 10 nM) with similar activity to that of Epalrestat. Structural analysis, especially by X-ray crystallography of two selected compounds, and molecular modeling comparisons with Zopolrestat were performed. These results provide explanations of the good activity of the inhibitor, the preference for 1-naphthyl-substituted compounds, and the nature of molecular interactions in these systems.

[Biotransformation of aza-3-chalcol in the rat: isolation and structural analysis of seven metabolites]. / Biotransformation de l'aza-3 chalcol chez le rat: isolement et analyse structurale de sept métabolites.

The azachalcol 3-phenyl-1-(3-pyridinyl)prop-2-en-1-ol S-1 has been used to investigate the metabolic profile in rat. Seven metabolites and the unchanged substance were isolated from urine. The biotransformation products were extracted and purified by chromatography (LC, CTLC, HPLC) and identified by comparison with some synthetic reference compounds or by spectroscopic analysis (UV, IR, 1H, 13C NMR and MS). A scheme of potential metabolic pathway is proposed. It appears that three specific targets of the parent molecule are extensively oxidized. Thus the aromatic heterocycle yields three N-oxides (M-4, M-5, M-7). The deshydrogenation of the secondary alcoholic group to the ketone is also observed (M-2). Finally, the ethylenic double bond is a favored site for hydroxylation (M-7, M-8) as well as reduction (M-3, M-4, M-6).

Antiinflammatory and immunostimulant activities of six sulphur compounds--four benzenesulphonates, levamisole, and pyritinol hydrochloride--assayed in mouse cell activation studies.

The effect of a phlogogenic agent and of six sulphur compounds on peritoneal macrophages, spleen B lymphocytes, and von Kupffer cells of the liver has been observed in BALB/C mice. The phlogogenic agent (0.5% carrageenin + 10% peptone) was a potent stimulant of the macrophages (increasing their number, protein content, and acid phosphatase activity), the lymphocytes (increase of haemolytic plaque counts), and the von Kupffer cells (increase of the colloidal carbon clearance rate which measures phagocytic capacity). Of four acid sulphur compounds (benzenesulphonates)-ethamsylate, diethylammonium persilate, calcium dobesilate, and piperazine sultosilate--not previously screened for antiinflammatory activity, all except piperazine sultosilate inhibited the macrophages, all except calcium dobesilate stimulated the lymphocytes, and only calcium dobesilate stimulated the von Kupffer cells. Two non-acid sulphur compounds--levamisole and pyritinol hydrochloride--had no effect on the macrophages but were potent stimulants of the lymphocytes and the von Kupffer cells. Because of these immunostimulant properties, levamisole and pyritinol hydrochloride may prove useful in the treatment of diseases such as rheumatoid arthritis in which the patient's immune potential has to be restored.

[Present data on inflammation. III. Experimentally induced inflammation (author's transl)]. / Aspect actuel de l'inflammation. III. L'inflammation expérimentale.

In a previous chapter, the importance of macrophages in inflammatory processes was emphasized upon. The authors now mention the outstanding inflammatory agents utilized for experimental purposes, especially as regards the pattern of their action. Finally, this paper restates the question of the pharmacology and therapy in inflammation.

[Effect of anti-inflammatory agent administration on Balb/c mouse peritoneal macrophage activity]. / Influence de l'administration d'anti-inflammatoires sur l'activité des macrophages péritonéaux de souris Balb/c.

A study of the mouse Balb/c peritoneal macrophages has been made after oral antiinflammatory drugs administration on animals which previously had an inflammation with carrageenan. The results show an enhancement of the number of the macrophages, of their enzymatic activities and of their proteins' content. These three parameters fall down more or less rapidly according to the considered antiinflammatory drug.