Development of novel chiral pyrrolidinebisphosphine ligands (BPPM, PPM etc.) from L-hydroxyproline and their application to catalytic asymmetric synthesis of biologically important compounds were described. α-Amino acid (91-92% optical yields), salsolidine (45%), α-hydroxyester (78.5%), R-(-)-pantolactone (80.5-86.7%), β-aminoacids (53-55.2%), α-methylsuccinic acid (94.2%), and β-methylaspartic acid (58.2%) were obtained. The mechanism of their asymmetric hydrogenation was also clarified.
The review on our recent works mainly consists of four parts in relation to biochemical pharmacology and toxicology, and metabolism of marihuana constituents, tetrahydrocannabinol as follows; 1) metabolic activation, 2) interactions with other central acting drugs, 3) development of tolerance and cross-tolerance, 4) other biological effects. Especially, the role of the active metabolites of tetrahydrocannabinol in the marihuana intoxication has been discussed in detail.
Two new compounds, cistanosides H (II) and I (III), were isolated from Cistanchis Herba, the whole plant of Cistanche salsa (C. A. MEY.) G. BECK (Orobanchaceae), together with a known compound, decaffeoylacteoside (I). The structures of II and III were determined to be 2-(3, 4-dihydroxyphenyl) ethyl O-H. Kobayashi, H. Karasawa, T. Miyase, S. Fukushima, Chem, Pharm. Bull., O-α-L-rhamnopyranosyl-(1→3)-2-O-acetyl-β-Dglucopyranoside and O-H. Kobayashi, H. Karasawa, T. Miyase, S. Fukushima, Chem, Pharm. Bull., -L-rhamnopyranosyl-(1→3)-(4-O-p-coumaroyl)-D-glucopyranose, respectively, on the basis of chemical and spectral data.
The title compounds (4a-t) were prepared from cis-2-aryl-(1H-imidazol-1-ylmethyl)-1, 3-dioxolane-4-methanol and the corresponding acyl chlorides. As for R1-phenyl group at the 2-position, 2, 4-di-substituted phenyl compounds (4j-t) showed strongeractivities than 4-substituted ones (4a-i) against Trichophyton and Aspergillus groups. With respect to the 4-substituent, 4-substituted benzoyloxymethyl compounds (4a, c, f, g, i-m) showed stronger antimicrobial activities against Fungi than 2, 4-dichlorobenzoyloxy analogues (4b, d, e, h, n). Compounds (41) showed the stronger activities among all compounds tested, and n-butylester derivative (4r) showed strong activities as well.
This paper describes a high-performance liquid chromatographic assay of trace amounts of sisomicin (SISO) in the plasma by the pre-column ultraviolet (UV)-derivatization with o-phthalaldehyde (OPA)/thioglycollic acid (TGA) reagent. The SISO was extracted from the plasma by using a CM-Sephadex column. The derivatization products were separated by the column-switching method consisting of a reversed-phase pre-column and an analytical column, and measured at 330nm with UVdetector. When applied to the drug monitoring in the rabbit plasma at a single dose of 1mg/kg (i. v.), the presented method was sensitive to 19ng of SISO base per column injected (500μl).
Squalene (SQ) which was highly purified from shark liver oil and its related compounds were tested for antitumor activity. SQ has no cytotoxic activity in vitro and in vivo, and showed rather high tumor growth inhibitory effect against sarcoma 180 by p.o. administration. It is due to host-mediated antitumor activity. SQ prevented lung metastasis in mice bearing Lewis lung carcinoma by p. o. administration and showed dominant effects by combination with other cancer therapy.
In order to disperse titanium dioxide (TiO2) powders (0.2μm) well in emulsion systcm, a surface modification of Nylon 12 powders (5μm) were applied.TiO2 and Nylon 12 powders were mixed to modify the surface of Nylon 12 powders with an automatic ceramic mortar. The strong adhesiveness of TiO2 powders to the surface of Nylon 12 powders was confirmed by an X-ray analysis and a scanning electron microscopic observation. The dispersibility of the particles was tested in water, liquid paraffin and emulsions. TiO2 powders were dispersed in neither water nor liquid paraffin, but Nylon 12 powders were dispersed well in the both solvents. TiO2 modified Nylon 12 particles (TiO2, 33%) showed the physicochemical properties, especially wettability, of both TiO2 and Nylon 12 powders, so the modified particles were dispersed well in liquid paraffin but not in water. In O/W type emulsion, only 0.3% TiO2 powders were aggregated but 1% of the modified particles (0.3% as TiO2) were dispersed well. On the other hand, in W/O type emulsion larger amount of the modified particles (5%) were dispersed well. It is concluded that the surface modification of Nylon 12 powders is a good method to disperse TiO2 powders well in emulsions, and especially W/O type emulsion containing the modified particles was suggested to be applicable to sun screen agents because of its good shielding effect from ultraviolet light.
Adaptation was attempted of the concentration-response equations proposed by Wagner to the pharmacokinetic and pharmacodynamic data obtained after oral administration of furosemide to healthy human subjects. The results revealed that a quantitative correlation between drug concentration and pharmacologic response decreases with the cumulation of diuretic response or cumulated urine volume.
The aim of this study was to evaluate the effect of water extract of “Reishi”, the fruit body of Ganoderma lucidum, cultivated in Nara prefecture ([L]) on the experimental allergic disease models. Inhibitory activity of [L] on histamine release from rat peritoneal mast cells induced by compound 48/80 or antigen (egg white albumin)-antibody reaction and on passive cutaneous anaphylaxis (PCA) reaction in guinea-pig and rats were investigated. Consequently, [L] inhibited significantly the histamine release induced by antigen in addition to the release induced by compound 48/80.[L] also showed an inhibitory effect on PCA reaction in guinea-pigs and rats. These findings indicated that [L] was effective on immunoglobulin E-related allergic reaction.
The anti-allergic activity of aqueous extract of “Reishi” ([L]), the fruit body of Ganoderma lucidum, was evaluated in the experimental models of allergy. [L] was found to prevent remarkably the experimental asthma in guinea pigs and contact dermatitis induced by picryl chloride in mice. It also exhibited markedly a therapeutic effect against the lesion of kidney and decreased the protein excretion into the urine, in serum sickness nephritis caused by immune complex in rats.
Lipid microspheres (LM) with 0.2μm in diameter possess properties as drug carriers resembling liposome. The interaction of LM with MM46 tumor cells in vitro was investigated for the application in drug delivery systems of antitumor drugs. LM were recognized by electron microscopy to be taken up by tumor cells. The uptake of LM by tumor cells increased when an anti-MM46 monoclonal antibody was added. The uptake of LM by the tumor cells increased about 3-fold by use of anti-MM46 monoclonal antibody and protein A which had been incorporated into the surface of LM. The results suggest that LM, particularly with the use of anticancer antibodies, is valuable in drug delivery systems for antitumor drugs.
The immunostimulant effects of some immunomodulators, including D-penicillamine levamisole, auranofin, lobenzarit, thiobutarit, Y-9577, mecobalamine, forphenicinol, Ge-132, TEI-3096, were investigated by using plaque forming cell assay in C3H/He aged mice and rosette forming cell assay in C57BL/6J mice. Both the assays showed similar results and all drugs except mecobalamine and forphenicinol augmented immune response. However, some immunomodulators had an optimal dose. The results of this study agreed well with the clinical effectiveness. In a subsequent experiment, the effects of concomitant administration of TEI-3096 and indomethacin, a prostaglandin synthesis inhibitor, were studied by use of rosette forming cell assay in C57BL/6J mice and the immunopotentiating effect of TEI-3096 was augmented when indomethacin was concomitantly administered. This results suggest that prostaglandin is one of the regulating factors in immune response and the combination therapy with immunomodulators and indomethacin is more efficient.
O-Phosphoethanolamine (PEA) was determined by cation exchange high-performance liquid chromatography in trichloroacetic acid extracts of spleens. An in-stream fluorometric detection system by using o-phthalaldehyde permitted the rapid analysis of samples containing 11.3-680.4 nmol/ml of PEA. The PEA concentration in mouse, rat, guinea pig, porcine and cattle spleens was determined. Spleens studied were found to vary widely in their PEA concentration showing species differences.