Ascamycin and dealanylascamycin, nucleoside antibiotics from Streptomyces sp.
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Biomedical subjects
Publications and source records attributed to N Miyata.
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A newly isolated strain of Streptomyces sp. produces a new nucleoside antibiotic, ascamycin and the corresponding dealanyl derivative. The structure of ascamycin was determined to be 2-chloro-9-beta-[5-O-(N-L-alanyl)sulfamoyl-D-ribofuranosyl]-adenine. Remarkable selective toxicity of ascamycin compared to the dealanyl derivative was accounted for on the basis of a dealanylating enzyme present in the envelope of sensitive bacteria. After dealanylation, it becomes permeable to cell membrane.
A new artificial blood substitute, FOB, which has been shown to be a good solvent for oxygen, contains a Bromine atom within its molecule. FOB is taken up in tumor macrophages and the Bromine shows opacity on X-ray film by absorbance of X-rays. In this study, tumor imaging possibilities were studied using conventional roentgenograms, on mice bearing transplanted Ehrlich ascites tumors on the right leg and which were given a 1-ml injection of 50 w/v % FOB. The results obtained follows: Solid Ehrlich tumors were imaged clearly wih injected FOB. X-ray films showed persisting homogeneous tumor staining, and irregular linear and plaque opacities. Larger tumors (more than 5,000 mm3 in volume) were imaged less clearly than smaller ones (about 1,000 mm3 in volume), because of superimposition of X-ray absorbance of the FOB taken up and of the larger tumor mass itself. The patterns of FOB taken up into the transplanted tumor were different according to various tumor growth time. Tumor imaging effect was enhanced by double time injection of 1 ml FOB. Histological features of Ehrlich tumors injected with FOB showed that FOB was phagocytosed by macrophages in the tumor tissue. The radiosensitization effect of FOB has already been reported by us. These results suggested that FOB acts not only as a sensitizer in radiation therapy, but also as a tumor imaging agent for diagnosis of the localization of malignancy in radiotherapeutic planning.
To enhance tissue PO2 of radioresistant hypoxic cells of tumor, artificial blood substitute (FOB) was applied, because it is excellent solvent for oxygen and allows the blood circulation system to recover and consequently increase the oxygen supply from blood to the tissue. When trasplanted Ehrlich tumor of mice on thigh grew about 1,000 mm3 in volume, those were divided into three groups, group 1: 60Co gamma-ray irradiation alone, group 2: irradiation under breathing oxygen, and group 3: irradiation under breathing oxygen after exchange transfusion with FOB. The radiosensitization of FOB was studied by comparing with the OER values of three groups for 50% TGD time, 50% SD time, and 50% and 75% TCP. The OER values of 50% TGD time, 5, 10 and 50% SD time 10 of oxygen group were 1.46, 1.29, and 1.22, respectively, and oxygen effect was observed in this group. Those values of FOB group were 2.02, 1.56, and 1.56, respectively and oxygen effect of FOB group was greater than those of oxygen effect of FOB group was greater than those of oxygen group. Animals receiving FOB were apparently radiosensitized by oxygen against animals breathing oxygen at small doses irradiation effect (50% TGD time, and 50% SD time). The OER values of 50% and 75% TCP at 30 days and 90 days after irradiation of oxygen group were about 1.5 (1.46-1.61) and these of FOB group about 1.3 (1.15-1.38). Radiosensitization by oxygen of animals receiving FOB was not clearly recognized against animals breathing oxygen in TCP effect at high dose irradiation. These results indicate that radioresistant hypoxic cells of tumor receiving artificial blood substitute (FOB) increase the sensitivity of 60Co gamma-ray irradiation, especially at small dose irradiation.
The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 X 10(-6) M). Morphine epoxide (up to 3 X 10(-5) M) did not influence the responses of rat vas deferens (epsilon-receptor) or rabbit vas deferens (kappa-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (mu-receptor) than in the mouse vas deference (delta-receptor). The inhibitory action of [Met]-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 X 10(-6) M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the mu-receptor in vitro.
Morphine-7,8-oxide (morphine epoxide) is assumed to be a metabolite of morphine. Morphine epoxide in antinociceptive action was practically as potent as morphine. The development of tolerance in antinociceptive action was slower in the rats treated with morphine epoxide than in the rats with morphine. Furthermore, morphine epoxide was less potent than morphine in the inhibition of abstinence syndrome.
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The time course of the concentration of cefmetazole (CMZ) in the serum and in skin and intestinal tissues was determined after a single intravenous injection of 2 g of the drug. CMZ moved into them well. Furthermore, 41 patients with postoperative wound infection (superficial in 29 and deep in 12) were treated with CMZ 2-4 g daily. Bacteriological examination of the lesions with simultaneously carried out. As a result, 101 strains of bacteria were isolated and identified. Mixed infection was found in 27 cases (65.9%). Fifteen strains (14.9%) of E. coli, 15 (14.9%) of B. fragilis, 7 (6.9%) of Klebsiella sp. and 7 (6.9%) of Proteus sp., were the main bacteria isolated. Eight cases (19.5%) had mixed infection of E. coli and B. fragilis. The committee (3 members) evaluated CMZ to be effective in 75.6% (31 of 41 cases) and bacteria disappeared in 60.5% (23 of 38 cases). The side effects observed were pyrosis and feeling of gastric malaise in 1 case. The results suggest that CMZ is useful, which exerts an excellent effect on postoperative wound infections.
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The mutagenicity of several K-region arene oxides was tested in histidine-dependent mutants of Salmonella typhimurium. Benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide as well as some substituted phenanthrene oxides were mutagenic in strains TA 1538 and TA 98 which detect frame-shift mutagens. Structure-activity relationships are discussed from the standpoint of chemical reactivity. The absence of direct correlation between electrophilic reactivity and mutagenicity may suggest that primilarily physical properties, such as relative position of the epoxide group and molecular shape of arene oxides, are important for the emergence of mutagenicity of arene oxides.
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