Three transformation products of maridomycin (MDM) III, a macrolide antibiotic, by Streptomyces lavendulae were isolated by silica gel and alumina chromatography, and designated as spots 1 (starting MDM III), 2, 3 and 4, in the order of their decreasing Rf values on thin-layer chromatogram. By mass- and NMR-spectrometry and thin-layer chromatography, spot 2 was identified as 18-dihydro-MDM III, spot 3 as 4''-depropionyl-MDM III, and spot 4 as 18-dihydro-4''-depropionyl-MDM III. The relationship between starting MDM III and these transformation products were also discussed.
Aminoglvcoside 3'-phosphotransferases I and II in three strains of Pseudomonas aeruginosa were studied in comparison with those in two strains of R factor-carrying Escherichia coli. The strain TI-13 of P. aeruginosa produced the former and strain H-9 the latter. Strain B-13 produced the both enzymes. The 3'-phosphotransferases of type I in P. aeruginosa TI-13, B-13 and E. coli K12 J5 R11-2 were different from each other in chromatographic behavior, molecular weight, pH optimum, and Ki. The 3'-phosphotransferase of type II in P. aeruginosa H-9 and E. coli JR66/W677 showed the same behavior.
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 on 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.
Yeast polysomes are very active for amino acid incorporation when supplemented with elongation factors and the different components required for elongation of the polypeptide chain. This polysomal system is suitable for the study of the individual steps of the elongation cycle and to test the effect of different inhibitors. Anisomycin, trichodermin, trichodermol, trichothecin, fusarenon X, sparsomycin and blasticidin S inhibit peptide bond formation on these polysomes, whereas diphtheria toxin, pederine, cycloheximide and cryptopleurine block translocation.
The synthesis, microbiological profile and in vivo effectiveness in laboratory animals of a series of cephalosporins having 7-acyl substituents derived from methylthioacetic acid are described. Structure-activity relationships examined include the effect of oxidation of the side-chain sulfur atom, replacement of the (side-chain) methyl hydrogens by fluorine and replacement of the 3-acetoxy substituent by thioheterocycles. One derivative, 7-trifluoromethylthioacetamido-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (SK&F 59962), was found to have outstanding antibacterial activity in vitro and in vivo.
SK&F 59962, a new parenteral cephalosporin was found to have a high order of in vitro and in vivo antibacterial activity against a broad-spectrum of clinical isolates. When tested in vitro against gram-negative organisms, SK&F 59962 was consistently more active than cefazolin and far superior to cephalothin. This new antibiotic had activity equal to that of cephalothin against gram-positive bacteria. Enterobacter species were found to be susceptible to SK&F 59962. In mouse infection studies using bacterial pathogens, SK&F 59962 had protective activity of the order of that of cefazolin and superior to that of cephalothin. Following parenteral administration the serum profile of SK&F 59962 in the mouse, dog and squirrel monkey was similar to that of cephalothin. SK&F 59962 and cephalothin had lower peak serum concentrations and shorter biologic half-lives than those of cefazolin.