Ibrahim R. Shimi

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.

Biosynthesis of itaconic acid by aspergillus terreus

SummaryThe formation of itaconic, aconitic and other acids from glucose in the presence of some enzyme inhibitors or organic acids by Aspergillus terreus was studied. Moreover, the metabolic activities of the preformed mats when floated on solutions of some organic acids were traced.When the resulting information were collected together a presumed condensation reaction between acetate and succinate could be formulated. The reaction product, presumably 1, 2, 3 propane tricarboxylic acid, would undergo a dehydrogenation reaction to yield aconitic acid and subsequently itaconic acid. It has also been suggested that aconityl CoA may be the metabolic form which suits the reactions leading to the formation of itaconic acid. The presumed aconityl CoA may be formed either through a condensation reaction between acetyl CoA and succinate or acetate with succinyl CoA.

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: C10H15N3O3; 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°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.

Studies on the synthesis of valine moiety of 6-aminopenicillanic acid by preformed mats of Penicillium chrysogenum.

Summary1.The formation of valine from acetone and glycine and from propan-2-ol and glycine was demonstrated. The transformation of propan-2-ol to acetone was suggested.2.Acetone, propan-2-ol, glycine, valine and cysteine stimulated the biosynthesis of 6-APA when supplemented separately to the medium. These compounds are arranged in a descending order with respect to their stimulative influence.3.Coenzyme A influenced favourably the formation of 6-APA.4.A mixture of acetone, glycine, and cysteine was the most stimulative among the other combinations tried.5.A presumed sequence of reactions between acetone, glycine and cysteine, probably involving CoA, was thus suggested for the biosynthesis of 6-APA. The reactions involve dehydration and dehydrogenation with the liberation of two molecules of water and two hydrogen atoms.

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.

Gluconimycin, a new antibiotic.

SummaryA new antibiotic, gluconimycin, was isolated from Streptomyces AS 9. The systematic position of the organism is discussed. Gluconimycin has a polypeptide nature. It contains iron and gluconic acid in its molecule. Thus it has been classified as a member of sideromycins. Gluconimycin is considered from the fast moving type when chromatographed by butanolacetic acid-water. The antibiotic is active against Gram+ve, Gram-ve bacteria and some fungi. The antibiotic exerts high toxicity when injected in mice.

Catabolism of itaconic acid by preformed mats of aspergillus terreus

SummaryThe breakdown of itaconic acid by preformed mats of a local strain of Aspergillus terreus was studied using the zone-strip technique. Low pH values restrained the uptake of itaconic acid and the accumulation of various other acids while higher pH values exerted an opposite effect. The results obtained when using various enzyme inhibitors were those anticipated on basis of the direct transformation of itaconic to aconitic acid through the fixation of CO2 and of the existence of the T.A.C. (tricarboxylic acid cycle) as a main metabolic channel operating in this organism.

The mechanism of action of cairomycin B

1. 1. Cairomycin B (CB) inhibits nucleic acid and protein synthesis in cells of Staphylococcus aureus. 2. 2. The antibiotic elevated the Tm of DNA while that of RNA was lowered. 3. 3. DNA dependent RNA polymerase was inhibited by the antibiotic. 4. 4. Sedimentation properties of DNA & RNA with CB showed an increase in their S values. Sedimentation analysis for mixtures left after Tm determination showed the same pattern as the unheated mixture containing DNA whereas that containing RNA revealed fewer fractions. 5. 5. The [3H]CB bound with [14C]DNA and with ribosomal RNA; mainly the 50 S subunits and the 70 S as well. 6. 6. CB was found to interfere with polypeptide chain elongation but not with the initiation step. 7. 7. Miscoding induced by CB during polypeptide synthesis through misreading of U as A in 5-terminal of UUU triplet was also demonstrated.

On the mode of action of ferramidochloromycin on bacillus subtilis

Abstract 1. 1. The effects of ferramidochloromycin (FACM) on a sensitive strain of Bacillus subtilis was examined. 2. 2. Ferrioxamine B failed to antagonize the antimicrobial effects of FACM. The antibiotic exerted no effect on the synthesis of lipids, RNA and DNA whereas it arrested protein synthesis through inhibiting lysyl tRNA synthetase and hence preventing the incorporation of [ 14 C]lysine. 3. 3. Treatment of B. subtilis with relatively high concentrations of FACM and for long incubation periods converted the cells from rod to cocci shape with the accumulation of N -acetyl aminosugars. The effect is presumably a secondary one.

In vitro liquefaction of human blood clots by metabolites of bacillus subtilis

SummaryThe influence exerted by some cultural conditions on the ability of metabolites of Bacillus subtilis to liquefy the human blood clots was studied. Crude enzyme preparations capable of liquefying the clots were isolated from the culture solutions. The aminoacids produced during the liquefaction process could be traced. Both of the enzyme preparation and the metabolism solution induced no obvious toxic effects when injected into veins of rabbits.