Biomedical subjects
Publications and source records attributed to T Kurihara.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Male Sprague-Dawley rats were fed a 0.1% ethionine-added choline-deficient diet for 8 weeks to induce liver cirrhosis. At the same time 100 mg/kg/day teprenone was administered orally in order to evaluate its effects on the liver and gastric mucosal blood flow. Blood flow increased not only in gastric mucosa but also in liver tissues in the teprenone group. Serum transaminase levels and histopathologic findings of the liver also improved. These findings suggest that teprenone alleviates hepatocellular injuries. This effect may be partly attributable to cytoprotective effects of the catenoid isoprenoid moiety of teprenone on liver cells.
The relationship between radical intensity and biological activity of cacao husk extracts was investigated. Electron spin resonance (ESR) spectroscopy demonstrated that the radical intensity of hexane, acetone, methanol and 70% methanol extracts increased with water-solubility. Several fractions of these husk extracts, separated by different column chromatographies, significantly inhibited the cytopathic effect of human immunodeficiency virus (HIV) infection in parallel with their radical intensity. However, their cytotoxic activity against human leukemic and carcinoma cell lines is not always correlated with their radical intensity. Water-soluble and lipophilic compounds might induce cytotoxic activity by different mechanisms.
We have previously reported on the diverse biological activities of benzo[a]phenothiazines, such as the induction of antitumor and antimutagenic activity in vivo, and differentiation and apoptosis in vitro. The relationship of radical generation and pi-spin density or dipole moment was investigated, using quantum-chemical calculation with UHF/PM3. These data suggest that the origin of radical generation by active benzo[a]phenothiazines, which affect such biological activities might be N-atom at position 12.
The antiproliferative activity of six "half-mustard type" phenothiazines against a total of 54 tumor cell lines: 4 leukemia, 9 non-small-cell lung, 7 colon-, 5 CNS-, 8 melanoma, 6 ovarian-, 8 renal-, 1 prostate and 6 breast cancer was determined by NCI-Information Intensive-Approach. The C-2 position of phenothiazines were substituted with H, Cl and CF3 groups. The half-mustard and ring system was linked either by a propylene or a butylene bridge. Colon-cancer cell showed the highest sensitivity against "half-mustard type" phenothiazines, followed by leukemia, melanoma, prostate-, CNS-, breast-, lung-, renal and ovarian cancer cells. These data suggest the "cancer-type-specific" antitumor action of "half-mustard type" phenothiazines.
Among 54 cancer cell lines, colon-cancer cells were the most sensitive to six "half-mustard type" phenothiazines [7-12], followed by leukemia, melanoma, prostate-, CNS-, breast-, lung-, renal and ovarian cancer cells. The distribution of electrostatic potential (ESP) of "half-mustard type" phenothiazines [7-12] suggests that the ESP surface of urea site is important for the interaction between "half-mustard type" phenothiazines [7-12] and target cancer cell structures (or DNA base sequence). Actually, the urea site of "half-mustard type" phenothiazines displayed extensive variability in the energy of lone pair orbital and net atomic charges of N1, 0 and N3 atoms.
Among twelve phenothiazine-related compounds, the cytotoxic activity of six "half-mustard type" phenothiazines [7-12] was significantly higher than that of six phthalimido compounds [1-6]. 1-(2-Chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)propylurea [9], 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)butylurea+ ++ [10] and 1-(2-chloroethyl)-3-(2-trifluoromethyl-10H-phenothiazin-10-yl)b utylurea [12] showed the highest cytotoxic activity, in parallel with high delta mu (difference between two dipole moments, mu g and mu e). There was also positive relationship between cytotoxic activity and molecular orbital energy such as pi-LUMO, pi-HOMO, and lone pair orbitals originated from O, N1, and N3 atoms. The present study demonstrated that cytotoxic activity of "half-mustard type" phenothiazines can be predicted by their dipole moments and molecular orbital energies.
Grape seed extracts were more cytotoxic than grape peel extracts. Methanol and 70% methanol extracts of grape seed selectively killed two human oral tumor cell lines, more efficiently than human gingival fibroblasts. ESR spectroscopy revealed that these extracts produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate at higher concentrations. On the other hand, lower concentration of these extracts slightly reduced the radical intensity of sodium ascorbate, and scavenged superoxide anion, generated by hypoxanthine and xanthine oxidase reaction. These properties of grape seed extracts suggest their possible application for cancer prevention.
Fractionated extracts of Feijoa peels were studied for cytotoxic activity, anti-human immunodeficiency virus (HIV) activity and antibacterial activity. Two most cytotoxic fractions A3 of acetone extract and M2 of methanol extract had potent inhibitory activity against Gram-positive and Gram-negative bacteria as well as fungi tested. Fraction A4 of acetone extract showed multidrug resistance (MDR)-reversal activity comparable with that of verapamil (positive control). These results indicate the therapeutic value of Feijoa peel extracts as potential antimicrobial and MDR-modulating agents.
Russian green sweet pepper (Anastasia Green) was successively extracted with hexane, acetone, methanol and 70% methanol and the extracts were further separated into a total of twenty fractions by silica gel or ODS column chromatographies. The biological activities of these extracts and fractions were compared. The extracts and fractions showed higher cytotoxic activity against two human oral tumor cell lines than against normal human gingival fibroblasts, suggesting their tumor-specific action. Several fractions [H3, H4, A4] reversed the multidrug resistant gene (MDR1) against L5178 mouse T-cell lymphoma more effectively than (+/-) verapamil (positive control). All extracts and fractions showed no anti-human immunodeficiency virus (HIV) nor anti-Helicobacter pylori activity. These data suggest the medicinal importance of an Anastasia Green extract.
In order to investigate the correlation between the carcinogenic activity of benz[c]acridines and the electron density, the Huckel orbital method was used. Resonance energies, circuit resonance energies and bond currents of benz[c]acridines were calculated by Aihara's TRE theory. It was shown that these compounds had very stable aromatic characters with positive resonance energies and that the resonance energies per pi-electron values for the compounds with lack of the double bond corresponding to the K-region from the parent skeleton were more stable than those of their parent compounds. 7-Methyl-benz[c]acridine derivatives with the methyl groups at 7-, 7, 9-, 7, 10-, 7, 11-, 7, 9, 10-, or 7, 9, 11-positions except 5, 7-dimethylbenz[c]acridine had potent carcinogenic activity and significantly lower resonance energy per pi-electron.
In order to study the correlation between the anti-tumor activity of benzo[a]phenothiazines and the electron densities, the Huckel orbital method and modified-neglect-of-diatomic overlap (MNDO) orbital method were used. 9-Methyl-12H-benzo[a]phenothiazine (2), which showed the most potent anticancer activity among benzo[a]phenothiazines, had the highest charge of nitrogen atom (QN), L-region (QL) and M-region (QM) in the molecule. The other derivatives, which showed weaker anticancer activity, had a much reduced value of these charges (QN, QL, QM). The data suggest that stability of pi-electron in 1 benzene ring and 1 naphthalene ring in the benzo[a]phenothiazine skeleton might be responsible for the induction of anticancer activity.
The abilities of 14 phenothiazines, 8 benzo[a]phenothiazines and 12 benz[c]acridines to induce an antibacterial effect against Escherichia coli K12 were compared. Several phenothiazines, which showed antiplasmid activity, displayed the most potent antibacterial activity. All benz[c]acridine derivatives were moderately antibacterial, whereas benzo[a]phenothiazines were inactive. The active phenothiazine derivatives had more potent inhibitory activity against fungi, including phytopathogen filamentous, human pathogen filamentous fungi and yeasts, than against gram-positive and -negative bacteria. Taken together with previously reported data, the induction mechanism of antimicrobial and antiplasmid activity by these compounds seems to be different from that of antitumor, differentiation-inducing and carcinogenic activity.
Various synthetic derivatives of phenothiazines, benzo[a]phenothiazines and benz[c]acridines were compared for their abilities to induce antiplasmid activity against E. coli F'lac plasmid. Several phenothiazine derivatives were much more potent in antiplasmid activity than benzo[a]phenothiazine- or benz[c]acridine derivatives. Their antiplasmid activity seemed to be enhanced by Cl- or CF3- substitution at 2 C atom, and modified by the side chain length and charge at the L-region of the molecules, as well as by hydrophilicity.
Interferon (IFN) is widely used to treat patients with chronic hepatitis types B and C but has been found to occasionally aggravate rheumatoid arthritis (RA) or cause interstitial pneumonia. We administered 6 MIU/d IFN-beta by intravenous injection for 6 weeks to a 55-year-old man with chronic active hepatitis type C associated with RA and interstitial pneumonia. Transaminase levels rapidly returned to normal after treatment and hepatitis C virus-RNA (nested RT-PCR method) was negative on completion of treatment. No significant adverse reactions or aggravation of RA or interstitial pneumonia occurred. These findings suggest that use of IFN-beta in the treatment of patients with chronic hepatitis type C associated with RA and/or interstitial pneumonia presents no problem if appropriate precautions are taken.