A degradation product of the chromophore of auromomycin.
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Biomedical subjects
Publications and source records attributed to Y Kumada.
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The protective effect of flunarizine against cerebral hypoxia-anoxia was investigated with various experimental models in mice and rats. The effect of flunarizine was compared with those of cinnarizine, verapamil and pentobarbital. The oral treatment of animals with flunarizine resulted in a consistent and long-lasting-protection against cerebral hypoxia-anoxia in all the models examined: Cytotoxic anoxia by KCN injection, hypercapnic anoxia induced by stopping artificial respiration, hypobaric hypoxia and normobaric hypoxia. The minimal effective dose of flunarizine was 1 to 20 mg/kg. The activity of flunarizine was 4 to 30 times as potent as that of cinnarizine and pentobarbital. Verapamil showed little or no protective effect. The mode of action of flunarizine was different from that of pentobarbital, which showed protection at anaesthetizing doses. These results indicate that flunarizine possesses a universal protective effect against cerebral hypoxia-anoxia, through the mechanism involved remains to be clarified. Hence, it is suggested that flunarizine might exert a beneficial effect on oxygen insufficiency of the brain resulting from cerebral ischemia.
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A new antitumor antibiotic, named auromomycin, was isolated from the culture broth of Streptomyces macromomyceticus, a macromomycin-producing strain. The antibiotic was recovered from the culture filtrate by salting out with ammonium sulfate and further purified by successive application of ion-exchange chromatography on Amberlite IRA-93 (Cl form) and DEAE-Sephadex (OH form), Gel filtration on Sephadex G-50 and hydrophobic chromatography on Octyl-Sepharose CL-4B. The antibiotic is an acidic polypeptide with a molecular weitht of 12,500 and an isoelectric point of pH 5.4 and consists of 16 different amino acids. It has characteristic absorption maxima at 273 nm and 357 nm in the ultraviolet spectrum and two minima at 280 nm and 350 nm in the optical rotatory dispersion spectrum. Auromomycin exhibits antibacterial activity not only against Gram-positive bacteria, but also Gram-negative bacteria. Antitumor activities of auromomycin were revealed against EHRLICH ascites carcinoma, ascites sarcoma 180, L1210 leukemia and LEWIS lung carcinoma. Auromomycin was found to be converted into macromomycin by adsorption chromatography on Amberlite XAD.
Isocoformycin is a structural isomer of coformycin which has been demonstrated to be a potent inhibitor of adenosine deaminase. Isocoformycin showed a weaker inhibition of this enzyme than coformycin; the binding of coformycin to enzyme was irreversible, but isocoformycin inhibition was competitive with substrate. The Ki value of isocoformycin was 4.5 approximately 10 X 10(-8) M. Following intraperitoneal injection of isocoformycin in mice, the adenosine deaminase activity of homogenates of several organs was determined and the following ED50 values (50% inhibition doses) were observed: 29 mg/kg for thymus, 13 mg/kg for spleen, 80 mg/kg for liver and 20 mg/kg for kidney. The inhibition of adenosine deaminase in rabbit blood in vitro was also tested in comparison with coformycin.
Activities of derivatives of dehydrodicaffeic acid dilactone (DDCAD) to inhibit catechol-O-methyltransferase (COMT), cyclic AMP phosphodiesterase (PDE) and DOPA decarboxylase (DDC) were examined. Among those tested, 2,6-bis-(5',6'-dibromo-4'-hydroxy-3'-methoxyphenyl)-3,7-dioxabicyclo-[3,3,0]-octane 4,8-dione was found to be the strongest inhibitor of both COMT and PDE. There were no derivatives which showed a stronger inhibition against DDC than the original compound, DDCAD.
In the screening of catechol-O-methyltransferase inhibitors, three compounds were isolated from the culture filtrate of a mushroom, Inonotus sp. One was 3,4-dihydroxycinnamic acid (caffeic acid) which had been reported as an inhibitor of this enzyme. The others were the dextrorotatory 2,6-bis-(3',4'-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]-octane 4,8-dione (dehydrodicaffeic acid dilactone) andits antipode. These new compounds inhibited both dopamine beta-hydroxylase and dopa decarboxylase and showed hypotensive activity in the SH rat.
In the screening of catechol-O-methyltransferase inhibitors in streptomyces culture filtrates, three new isoflavones were isolated. Their structures were shown to be 3',5,7-trihydroxy-4',6-dimethoxyisoflavone (I), 3',5,7-trihydroxy-4',8-dimethoxyisoflavone (II), 3',8-dihydroxy-4',6,7-trimethoxyisoflavone (III). I and II inhibited both catechol-O-methyltransferase and dopa decarboxylase, and showed hypotensive action. III was a specific inhibitor of catechol-O-methyltransferase, and showed no hypotensive action.
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