BL-P 875, a new semisynthetic penicillin, was found to possess broadspectrum antibacterial activity. Its inhibitory potency for both gram-negative and gram-positive organisms was comparable in all respects to that of ampicillin. Despite this, BL-P 875 proved to be significantly more active than ampicillin when administered by the oral route in a number of experimental bacterial infections of the mouse. Median curative doses (CD50) of BL-P 875 in infections produced by Streptococcus pyogenes, Klebsiella pneumoniae, Proteus mirabilis, and 1 of 2 Escherichia coli strains were less than one-half those of ampicillin. On the other hand, comparable doses were required for curing mice challenged with Staphylococcus aureus, Diplococcus pneumoniae, or Salmonella enteritidis. Since no differences in acid stability, bactericidal effect, or serum binding were found for the 2 compounds, the probable explanation for BL-P 875's superior therapeutic activity is its higher degree of oral absorbability. BL-P 875 concentrations in mouse blood after oral administration were significantly higher (about 2-fold) than those of ampicillin at both one-half and 1 hour post-administration. Greater absorbability was also found in rats, where about twice as much BL-P 875 as ampicillin was recovered from urine after administration of a single oral dose. No differences in mouse blood levels or urine recovery values could be demonstrated for the parenterally-administered antibiotics.
Isolation of a series of antibiotics produced by a new variety of Streptomyces viridochromogenes was attempted, and three main components were obtained as amorphous powders. They were primarily active against Grampositive bacteria, anaerobic bacteria and mycoplasma and characterized as new members of sulfur-containing peptidic antibiotics. The antibiotic complex was named sulfomycin.
In our screening for antitumor antibiotics using the Ehrlich ascites tumor, acetone extracts of the mycelia of Penicillium crustosum, Penicillium tardum, Cephalosporium diospyri and Sepedonium ampullosporum showed significant antitumor activity. These fungi were selected because of cytotoxicity or antiviral activity on chick embryo fibroblast cell monolayers. The extracts were fractionated by silica gel column chromatography and the active principles were obtained as colorless oils which showed the characteristic infrared absorption bands of long-chain fatty acids. The active principles exert marked antitumor activity against EHRLICH ascites tumor, although they showed neither antiviral activity nor inhibitory activity against microorganisms.
The isolation of antitumor active oily substances from the mycelia of Penicillium crustosum, Penicillium tardum, Cephalosporium diospyri and Sepedonium ampullosprum has been described previously. The present paper describes chemical studies on these active products. Their infrared absorption spectra were virtually identical and were typical of long-chain fatty acids.Nuclear magnetic resonance spectra confirmed the presence of long-chain methylene and methylene interrupted double bonds. Mass spectra and the gas chromatographic studies of the methyl esters indicated the presence of palmitic, octadecaenoic and octadecadienoic acids as major constituents.
The fate of the orally effective antibiotic D-cephaloglycin and its much less active L-enantiomer has been studied in the rat. D-Cephaloglycin-14C is metabolized by two pathways, (1) hydrolysis of the amide linkage to form D-2-phenylglycine-14C and (2) deacetylation to form deacetyl-D-cephaloglycin-14C. D-Cephaloglycin is absorbed from the gastro-intestinal tract at least in part as the intact antibiotic, L-Cephaloglycin-14C is rapidly metabolized to L-2-phenylglycine-14C and its metabolites. In contrast to the results with D-cephaloglycin-14C, no intact L-cephaloglycin-14C or deacetyl-L-cephaloglycin was excreted in the urine of rats.