X-14547A is a novel antibiotic produced by a new strain of Streptomyces antibioticus (NRRL 8167). The antibiotic is active in vitro against Gram-positive bacteria and is capable of complexing and transporting divalent as well as monovalent metal cations.
A novel carboxylic acid ionophore, antibiotic X-14547A, closely related to the polyether antibiotics has been isolated along with four other metabolites from fermented cultures of a new strain of Streptomyces antibioticus. The structure, determined by X-ray analysis of the R(+)-1-amino-1-(4-bromophenyl)-ethane salt contained pyrrole carbonyl and trans-butadienyl chromophores in addition to the unusual tetrahydroindane bicyclic ring system. A second novel metabolite was identified as 3-ethyl-1, 3-dihydro-3-methoxy-2H-indol-2-one.
A 17002 C is a new metabolite produced by Actinoplanes strains, structurally related to the virginiamycin factor M. On the basis of physico-chemical data, MS, IR, 1H and 13C NMR, structure I is assigned to A 17002 C.
Permetin A was purified from the culture filtrate of Bacillus circulans AJ 3902 by extraction with n-butanol, precipitation with sodium helianthate, CM-cellulose column chromatography and Sephadex LH-20 column chromatography. The compound was found to be anew peptide antibiotic containing 2, 4-diaminobutyric acid (Dab), leucine, isoleucine, phenylalanine, valine, serine (in a molar ratio of 3:2:1:1:1:1) and a fatty acid. This antibiotic showed activity in vitro against Gram-negative, Gram-positive and some anaerobic bacteria.
The structure of permetin A(I), an antibiotic substance produced by Bacillus circalans AJ 3902, has been elucidated as a cyclic acyl peptide by means of the mass and nuclear magnetic resonance spectroscopic techniques. C2H5CH-CH-CH2-CO-L-DCb-L-Ile→L-Dob→D-Phe CH3O L-Ser←L-Leu←D-Val←L-Dab←L-Leu The structure was found to be the same as polypeptin A(II) except that L-Thr in II is replaced by L-Ser in I. Details of the structural determination are given for the permetin A itself as well as for the hydrolyzed permetin A. C2H5CH-CH-CH2-CO→L-Dab→L-Ile→L-Dab→D-Phe CH3 O L-Thr←L-Leu←D-VoI←L-Dob-L-Leu II
A crystalline antibiotic, which we have named crinipellin, was isolated from submerged cultures of the basidiomycete Crinipellis stipitaria, strain No. 7612. High resolution mass spectrometry yielded the formula C22H28O5. The antibiotic is most active against Gram-positive bacteria, although yeasts and filamentous fungi are affected to a lesser extent. Crinipellin exhibits high in vitro inhibitory activity against the ascitic form of EHRLICH carcinoma. The incorporation of precursors of DNA-, RNA-, and protein syntheses in EHRLICH carcinoma (and in Bacillus brevis) cells was completely inhibited at 5(10) μg/ml. In Bacillus brevis the inhibition of the incorporation of uridine was found to be due to an interference by crinipellin with the transport of the precursor into the cells.
Methylated and acetylated derivatives of iturin A and mycosubtilin and methylated derivatives of bacillomycin L were prepared and their antibacterial activity on Micrococcus luteus was compared with the activity of the original substance. The results obtained show the importance of polar groups for the antibiotic activity of the substances of iturin group.
Cell-free preparations of Streptomyces nogalater and rat liver catalyze reduced pyridine nucleotide dependent conversion of nogalamycin to 7-deoxynogalarol and nogalose (Scheme 1). The mammalian process requires TPNH and has a specific activity of 85 nmoles of 7-deoxynogalarol formed per hour per mg of protein while the bacterial process prefers DPNH and has a specific activity of 5. The oxygen-sensitive conversions have pH optima of 7.5 (rat) and 9 (S. nogalater). Other anthracycline substrates converted to their 7-deoxyaglycones by both systems include nogamycin, 7(R)-O-methylnogarol, 7(R)-O-methylnogalarol, doxorubicin (Adriamycin), steffimycin, and steffimycin B.
The in vitro activity of Bay K-4999, 6[D-2-(3-furfurylidenamino-2-oxo-imidazolidine-1-carboxamido)-2-(4-hydroxy-phenyl) acetamido] penicillinate, a new ureido penicillin was evaluated against 555 clinical isolates and compared to selected β-lactams. Bay K-4999 inhibited most streptococci at concentrations less than I μg/ml, but was not active against β-lactamase producing Staphylococcus aureus. The activity of Bay K-4999 against streptococci including Streptococcus faecalis was similar to the activity of ampicillin. β-Lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by Bay K-4999; albeit at levels higher than needed for non-β-lactamasep roducing isolates. The activity of Bay K-4999 against the members of the Enterobacteriaceae varied from family to family and seemed to correlate with the presence of β-lactamases. Bay K-4999 was more active than ampicillin, piperacillin or mezlocillin against Escherichia coli lacking β-lactamases. It was more active against Klebsiella than piperacillin or mezlocillin, but cefazolin-resistant strains were not inhibited. It had activity against Pseudotonas aeruginosa comparable to piperacillin but was less active against Bacteroides fragilis. Bay K-4999 was hydrolyzed by β-lactamases of S. aureus, and by both plasmid and chromosomally-mediated β-lactamases of Enterobacteriaceae at rates comparable to ampicillin. It acted synergistically with gentamicin to inhibit resistant Pseudomonas isolates.
Skeletal muscle actin was found by centrifugation, turbidity, and viscosity measurements to form polymers upon addition of aminoglycosides, viomycin, polymyxin B, and tetracycline. A linear relationship was observed between the amount of actin polymerization and the number of primary amino groups on the aminoglycoside antibiotics except kanamycin. Of the antibiotics studied, neomycin was most efficient in actin polymerization. Polymerization of actin was not significantly induced by kasugamycin, chloramphenicol, erythromycin, benzylpenicillin, angustmycin A, formycin, actinomycin D, and mitomycin C. Aminoglycosides and viomycin were demonstrated to inhibit the acto-HMM Mg2+-ATPase reaction but did not significantly affect HMM Mg2+-ATPase activity. It was found by equilibrium dialysis that [3H]dihydrostreptomycin bound to actin.
The effects of primycin on mitochondrial respiration, volume changes, ATPase activity and the acidification following ATP hydrolysis were studied. Primycin in concentrations below 2-3 nmoles/mg mitochondrial protein reacts only with energized mitochondria rendering their inner membrane permeable to K+, Na+, Tris+ but not to TEA+. Above this concentration primycin interacts both with energized and deenergized mitochondria and the inner membrane also becomes permeable for H+, Cl- but not for ATP. In this case mitochondria very probably lose Mg2+. It is concluded that primycin up to concentrations of 2-3 nmoles/mg mitochondrial protein acts like an ionophore, while at higher concentrations it changes the permeability properties of the mitochondrial inner membrane without a drastic alteration of the membrane itself.