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Biomedical subjects

I R Shimi

Publications and source records attributed to I R Shimi.

At least 19 recordsLinked to original sources

Nilemycin, an intercalating agent for deoxyribonucleic acid.

1. Nilemycin (NM) is found to exert an inhibitory effect on the mouse tumor Sarcoma 180 near toxic doses but not with Leukemia 1210. 2. In Yoshida rat sarcoma cells NM inhibits cellular de novo nucleic acid synthesis and protein to a much lesser extent. 3. More than 50% inhibition by NM to de novo synthesis of RNA, in a system using calf thymus DNA as a template, could be observed. 4. Suitable levels of NM reduce the S values of DNA. 5. The antibiotic induced metachromatic changes in the u.v. spectrum of DNA solutions. 6. NM markedly inhibited the polynucleotide ligase repairing action on DNase-1-nicked DNA. 7. It is presumed that NM intercalates nicked DNA into such a configuration that the reactive sites of the polynucleotides are inaccessible to the ligase activities.

Animals↗

A new antitumour substance, 7-oxabicyclo (2.2.1)-5-heptene-2,3-dicarboxylic anhydride.

7-Oxabicyclo(2.2.1)-5-heptene-2,3-dicarboxylic anhydride has been found to possess antitumour activity against Ehrlich ascites carcinoma cells. The tumour cells incubated with the drug showed a decrease in the viable counts and cell proliferation. These effects were confirmed by in vivo studies in Swiss albino mice. The compound has a direct cytotoxic effect on the tumour cells. Vacuolization and disruption of the cytoplasm accompanied by unequal nuclear division and scattered chromosomes were recorded. In addition, 250 and 10 mg/kg were found to be the MTD and MED respectively. A dose of 25 mg/kg injected i.p. for 5 consecutive days in the tumour-transplanted animals caused a significant increase in their survival period. The compound has been shown to have a significant inhibitory effect on the DNA and RNA biosynthesis of EAC cells after 3 hr of administration; the protein biosynthesis was less affected. Meanwhile, the cellular contents of these metabolites were significantly reduced.

Animals↗

Isolation of cairomycins A and C.

Cairomycin B in the fermentation broths of Streptomyces sp. strain AS-C-19 accompanied cairomycin A and cairomycin C. The cairomycins are peptides with potent activity against gram-positive bacteria. On acid hydrolysis, cairomycin A yielded valine and aspartic acid, whereas cairomycin C yielded lysine, glycine, valine, leucine, and aspartic acid, as identified by paper and gas chromatography. These amino acids were found to exist in their alpha-L form. Cairomycin A was tentatively assigned a 6-isopropyl-2,5-diketopiperazine-3-acetic acid structure. The three cairomycins were distinct from each other in their ultraviolet, infrared, and mass spectra; elemental analyses; and their chromatographic behavior in different developing solvents.

Amino Acids↗

The mechanism of action of polychlorosubtilin.

Polychlorosubtilin (PCS) inhibits the growth of Escherichia coli. The antibiotic affected neither respiration nor glycolysis while the synthesis of nucleic acids and proteins were feebly hindered. Formation of aminoacyl-tRNA, peptide bonds and translocation from A to P sites of ribosomes were insignificantly influenced by the drug. The antibiotic exerted its effect(s) on ribosomes by interfering with the 30 S subunits. The 23 S and 30 SP were both sensitive to the drug but the latter was more obviously affected. Changes after developing resistance to the drug by the bacteria were localized in the 30 SP, 23 S and accordingly the 30 S subunits. The principal action of PCS was to cause multisited miscoding upon the incorporation of labeled aminoacyl-tRNA, therefore, malformed protein fractions (abnormal) were synthesized. As a natural consequence such abnormal fractions would not be expected to manifest the vital metabolic activities in the normal way.

Amino Acids↗

Staphcoccomycin, a new basic macrolide antibiotic.

Staphcoccomycin (SCM) is a new member of the basic macrolide family of antibiotics which was isolated from the fermentation broth of Streptomyces sp. AS-NG 16. The production, purification and determination of physical and chemical properties of this novel metabolite have been completed. Comparison of the mass fragmentation patterns of SCM and its peracetate with those of angolamycin peracetate suggested a des-mycarosyl derivative of angolamycin. Moreover, the molecular ion peak (m/e 771) corresponded to C39H65NO14 and the 1H-NMR of SCM was also consistent with the proposed structure.

Animals↗

Cairomycin B, a new antibiotic.

Cairomycin B is a new cyclic peptide antibiotic that was isolated from Streptomyces As-C-19 obtained from the soil of Cairo. The antibiotic had the following empirical formula: C(10)H(15)N(3)O(3); on acid hydrolysis, it yielded aspartic acid and lysine. Spectral analysis and its chemical characteristics indicated that it was a cyclic peptide. The antibiotic melted at 120 to 121 degrees C and was freely soluble in chloroform, ethyl acetate, and acetone, slightly soluble in alcohols, and rather insoluble in water and petroleum ether. Cairomycin B was mainly active against gram-positive bacteria, with high toxicity to experimental animals and weak serum-binding properties.

Animals↗

Kuwaitimycin, effect on synthesis of lipids in Bacillus subtillis cells.

The effects exerted by kuwaitimycin on synthesis of lipids as well as some metabolic activities of Bacillus subtilis were studied. The antibiotic not only arrested the inocrporation of 14C-acetate into the microbial lipids but also altered the fatty acids pattern, contents of i-C 15, a-C 15, i-C 17 and a-C 17 WERE MARKEDLY REDUCED, CONCOMITANT WITH AN INCREASE IN THE CONtents of i-C 14 AND N-C 14. Moreover, the rates of synthesis of phospholipids were decreased by the drug, especially that of phosphatidyl ethanolamine.

Anti-Bacterial Agents↗

4,4'-isopropylidine-bis(2-isopropyl)phenol, a new inhibitor for cell wall formation of Bacillus subtilis.

4,4'-Isopropylidine-bis[2-isopropyl]phenol was found to possess antimicrobial activity against gram-positive bacteria and some fungi, whereas it had no effect on gram-negative organisms. The drug has a potent inhibitory action on the synthesis of cell wall mucopeptides of Bacillus subtilis by inhibiting the enzyme d-glutamate ligase, which is responsible for the incorporation of d-glutamic acid into uridine 5'-diphosphate-muramyl-l-alanine. The drug had a weak lytic effect on protoplasts and inhibited protein synthesis, whereas no significant effect on the synthesis of deoxyribonucleic acid and ribonucleic acid was found.

Alanine↗

The mode of action of ASK-753 on Bacillus subtilis.

The mode of action of ASK-753 on Bacillus subtilis was examined. Unlike proper sideromycin antibiotics ferrioxamine B failed to antagonize the antimicrobial effects of ASK-753. The antibiotic could inhibit the biosynthesis of nucleic acids; effect on the RNA was more pronounced. ASK-753 affected the stability of prelabelled DNA of B, subtilis in growing or resting cultures; the effect on the latter was more pronounced. Lysis of B, subtilis protoplasts could be attained at 30 degrees C but not at 4 degrees C which excludes a possible detergent affect of the drug. The drug exerted a potent inhibiting influence on protein synthesis by arresting the activity of lysyl-tRNA synthetase and thus could prevent the incorporation of 14C-lysine.

Anti-Bacterial Agents↗

On the effect of N-methyl-bis (3-mesyloxypropyl) amine hydroxychloride on Bacillus subtilis cells.

N-Methyl-bis (3-mesyloxypropyl)amine hydrochloride is now in use as an antitumer drug. In view of its activity against some bacteria the present work was conducted to study its mode of action of Bacillus subtilis. The compound was found to induce irreversible damage to bacterial DNA whereas its effect on RNA was temporary and depending on maintenance of effective concentrations of the compound.

Antineoplastic Agents↗