An appropriate concentration of DNP (2, 4-dinitrophenol) is capable of inhibiting the ATP energized mitochondrial volume change induced by gramicidin in the presence of the permeant ions potassium and L-malate. The further addition of the non-mercurial thiol reagent, showdomycin reinstates, an effect of gramicidin which is dependent upon potassium ion. Thus the strategically located nucleophilic mitochondrial thiol group exposed by DNP occupies a pivotal position between two cycles. One of the cycles meshes with the respiratory chain and the other cycle meshes with ATP. This latter cycle contains the site sensitive to gramicidin.
A new antibiotic, funiculosin, C27H41NO7, was isolated from the filter cake of the fermented broth of Penicillium funiculosum THOM. Funiculosin is a neutral lipophilic substance which inhibits both DNA and RNA viruses as tested in infected primary chick embryo fibroblast cell monolayer and also some pathogenic fungi such as Tricophyton mentagrophytes and Candida albicans.
The metabolic fate of the orally effective antibiotic, cephalexin, has been studied in the rat and the mouse. Cephalexin is efficiently absorbed from the gastrointestinal tract as the intact antibiotic. Cephalexin is not metabolized in the body and is eliminated as unaltered antibiotic primarily via the urine. Cephalexin is more rapidly absorbed and eliminated by the mouse than by the rat.
Dextrochrysin is produced in culture broths of Streptomyces calvus var. dextrochrysus, and can be isolated in crystalline form by solvent extraction and silica gel column chromatography. It is obtained as neutral yellowish brown platelets, m. p. 250-255°C and shows strong dextrorotation. It has antimicrobial activity against Gram-positive and Gram-negative bacteria, a Mycobacterium and some bacteriophages, but is highly toxic to mice. In in vivo anti-tumor test with EHRLICH carcinoma and YOSHIDA sarcoma cells it did not show a favorable effect.
α, β-Diaminobutyric acid, isolated from the acid hydrolysate of aspartocin, was resolved into two of the four possible isomers with a Technicon amino acid autoanalyzer. ORD and NMR studies of the isolated isomers indicated that one had the D-erythro and the other the L-threo configuration. The difference in NMR spectra of the two isomers was quite likely a consequence of restricted rotation about the Cα-Cβ bonds due to electrostatic repulsion of charged amino groups. Whether the antibiotic contains both isomers or one was formed by racemization during hydrolysis was not determined.
A new antifungal substance, gougeroxymycin (m. p. 103°-105°C, λmax 234 -235 mμ in methanol) has been isolated from a Streptomyces. Production, isolation, physico-chemical, and biological properties of the antibiotic are described.
A new antibiotic, coriolin, was isolated from a Basidiomycetes, Coriolus consors. Coriolin is extracted with ethyl acetate from the cultured broth and crystallized as colorless needles, m. p. 175-176°C, C15H20O5. It inhibits growth of Gram-positive bacteria and Trichomonas vaginalis.
A new antitumor antibiotic is produced in fermentation broths by Streptomyces sp. S-66. This material, named lymphomycin, was isolated on the basis of inhibition of mouse leukemia SN-36 in mice, and toxicity to BURKITT lymphoma cells in tissue culture. It was precipitated from filtered broth with ammonium sulfate and purified by chromatography on columns of Sephadex and carboxymethyl cellulose. Lymphomycin is a black-colored, acidic protein with a molecular weight of about 11, 000 and valine as an N-terminal amino-acid. It contains no carbohydrates or nucleic acids. It is soluble in water, insoluble in most organic solvents, and is relatively stable in water over the pH range, 5 to 7. It has no distinct absorption maximum in its spectrum. Lymphomycin has no inhibitory activity against bacteria, yeast, fungi and mycoplasmas tested so far. It is cytotoxic to Burkitt lymphoma and human lymphoblastoid cells and peritoneal macrophages, but not inhibitory to human epidermoid carcinoma HeLa, mouse fibroblast L, chick embryo, calf kidney and mouse adenocarcinoma FM3A cells in tissue culture. Lymphomycin is lethal to tumor-bearing mice at 80mg/kg of body weight per day when given intraperitoneally once daily for 6 days, but not toxic at 40mg/kg/day. Tests with transplanted rodent tumors indicate that the antibiotic is inhibitory to the growth of both solid and ascitic forms of Sarcoma 180 and lymphatic leukemia SN-36 in mice. The growth of solid tumor of a fibrosarcoma in hamsters was also inhibited at optimal daily doses of 0.8 and 2mg/kg. Lymphomycin has no effect on the growth of the solid forms of EHRLICH and BASHFORD carcinoma in mice.