The kapurimycins, new antitumor antibiotics produced by Streptomyces. Producing organism, fermentation, isolation and biological activities

As a result of screening for antitumor agents from actinomycetes, the kepurimycins were isolated from Streptomyces sp. DO-115. The antibiotics were produced in a fermentation medium supplemented with high porous polymer resin which adsorbs antibiotics and results in an increase of titer. The active complex was isolated from the polymer resin by a solvent extraction procedure and was separated by column chromatography, into two minor and one major component, named A1, A2 and A3. The kepurimycins were active against bacteria, particularly Gram-positive organisms, and were cytotoxic to HeLa S3 human cerivical cancer cells and T24 human bladder carcinoma cells in vitro. Among the individual components of the kapurimycins, kapurimycin A3 exhibited the strongest antibacterial and cytotoxic activities. It showed a potent antitumor activity against murine leukemia P388 in vivo.     

Sapurimycin, new antitumor antibiotic produced by Streptomyces. Structure determination

The structure of a new anthra-gamma-pyrone antitumor antibiotic sapurimycin was determined by the spectral studies of its methyl ester. Sapurimycin has the same anthra-gamma-pyrone skeleton as pluramycin, but is distinctly different because of the absence of sugars on the D ring and possessing a carboxylmethyl group on C-5.     

Thrazarine, a new antitumor antibiotic. II. Physico-chemical properties and structure determination

A new antitumor antibiotic thrazarine was soluble in water and positive to anisaldehyde-sulfuric acid and ninhydrin color reactions. The absolute structure of thrazarine was determined to be O-[3R)-2-diazo-3-hydroxybutyryl)-L-serine by acid hydrolysis, spectroscopic analysis and X-ray crystallographic analysis. Structurally, thrazarine was a new member of azaserine group antibiotics.     

Bagougeramines A and B, new nucleoside antibiotics produced by a strain of Bacillus circulans. II. Physico-chemical properties and structure determination

Bagougeramines A and B obtained as sulfates were soluble in water and positive to Sakaguchi, chlorine-tolidine and ninhydrin color reactions. Their structures were determined by acid hydrolysis and spectroscopic analysis. Structurally they were closely related to gougerotin and they contained the guanidino-D-alanine instead of the serine residue in gougerotin. Bagougeramine B had the spermidine instead of the 6'-NH2 in structure of bagougeramine A.     

Duocarmycins, new antitumor antibiotics produced by Streptomyces; producing organisms and improved production

Six duocarmycins have been discovered during our search for new antitumor antibiotics and they showed extremely potent cytotoxic activity with IC50 values of 10(-12) M-10(-9) M on HeLa S3 cell. Three different producing strains isolated from soils were taxonomically assigned as Streptomyces. Duocarmycin A was unstable in culture broth, so improved culture conditions were designed to produce a high titer of duocarmycins B1, B2, C1 and C2 which are halogenated seco-compounds of duocarmycin A. Duocarmycin SA, one of the most potent cytotoxic agents yet discovered, was shown to be more stable in culture media than duocarmycin A, despite the structural similarity on their spirocyclopropylhexadienone moiety. In contrast to the duocarmycin A fermentation, no halogenated seco-compounds of duocarmycin SA were detected in culture broth supplemented with Br- or Cl-. All duocarmycins could be produced using one producing strain with improved media and culture conditions.     

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. II. Physico-chemical properties and structure elucidation

The structures of new antifungal antibiotics, PF1163A and B, were elucidated by spectroscopic analyses of the degradation products and by X-ray crystallography of the de-2-hydroxyethyl derivative of PF1163B. Both antibiotics consist of a 13-membered macrocyclic structure containing a derivative of N-methyl tyrosine and a hydroxy fatty acid. PF1163A differs from PF 1163B by having an additional hydroxyl group on the side chain.     

Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. II. Physico-chemical properties and structure determination

The structure of a new antitumor antibiotic, myrocin C, from a strain of Myrothecium verrucaria was characterized as a pentacyclic pimarane diterpene composed of a gamma-lactol group and a unique cyclopropane ring on the basis of its physico-chemical properties and spectroscopic data as well as a single-crystal X-ray diffraction analysis of its monoacetyl derivative.     

Sapurimycin, new antitumor antibiotic produced by Streptomyces. Producing organism, fermentation, isolation and biological properties

In screening actinomycetes for antitumor compounds, Streptomyces sp. DO-116 was found to produce a new antitumor antibiotic sapurimycin. It is structurally related to, but distinct from, kapurimycins. The antibiotic was produced in a fermentation medium supplemented with high porous polymer resin which adsorbs antibiotic in the culture and results in an increase of titer. Active material was separated from the polymer resin by a solvent extraction procedure and isolated by repeated solvent extraction, adsorption chromatography and HPLC. Sapurimycin was active against bacteria, particularly Gram-positive organisms. It exhibited antitumor activity against leukemia P388 and sarcoma 180 in mice. Sapurimycin caused single strand breaks in supercoiled plasmid DNA in vitro. These results are discussed in comparison with data for kapurimycins.     

Watasemycins A and B,new antibiotics produced by Streptomyces sp. TP-A0597

Two novel antibiotics, watasemycins A and B, were isolated from the fermentation broth of an actinomycete strain. The producing strain TP-A0597 was isolated from the seawater sample collected in Toyama Bay, Japan and identified as Streptomyces sp. based on the taxonomic study. The new antibiotics were obtained by solvent extraction and chromatographic purification and spectroscopic analyses identified that they were new analogs of thiazostatins. Watasemycin possesses a methyl group at 5'-position of thiazostatin instead of a hydrogen atom. Watasemycins showed antibiotic activity against Gram-positive and negative bacteria and yeast.     

Radamycin,a novel thiopeptide produced by streptomyces sp. RSP9. II. Physico-chemical properties and structure determination

The new cyclic peptide antibiotic, radamycin (1) and the known thiopeptide methylsulfomycin I (2) have been isolated from the fermentation broth of a Streptomyces sp. RSP9. The structure of radamycin was elucidated by NMR, LC-MS and FAB-MS and was established as a thiopeptide with oxazole and thiazole moieties, and several unusual amino acids.     

Nanaomycins, new antibiotics produced by a strain of Streptomyces. I. Taxonomy, isolation, characterization and biological properties.

Nanomycins are new antibiotics produced by the strain OS-3966 which was designated Streptomyces rosa var. notoensis. Nanomycins A and B were isolated from the culture filtrate by extraction with organic solvent and silica gel chromatography. The physical and chemical properties suggest that nanaomycins A and B are quinone-related compounds having the molecular formulae, C16H14O6 and C16H16O7, respectively. Nanaomycins A and B inhibit mainly mycoplasmas, fungi and Gram-positive bacteria. The acute toxicities (LD50, ip) of nanaomycins A and B in mice are 28.2 and 169 mg/kg, respectively.     

IB-96212, a novel cytotoxic macrolide produced by a marine Micromonospora. II. Physico-chemical properties and structure determination

IB-96212, is a new member of spiroketal containing macrolide class of fermentation-derived natural products isolated from mycelial extracts of Micromonospora sp. The structure consists of a new aglycone which possesses a 26-membered macrolide ring system and of one deoxy sugar identified as L-rhodinose, this structure represents the first reported spiroketal macrolide natural product related to other macrolides, such as oligomycins, dunaimycins, citovaricin, rutamycin and ossamycin.     

44-Homooligomycins A and B, new antitumor antibiotics from Streptomyces bottropensis. Producing organism, fermentation, isolation, structure elucidation and biological properties.

Oligomycin antibiotics, 44-homooligomycin A (NK86-0279 II) and B (NK86-0279 I) are newly discovered antitumor antibiotics with the substitution of ethyl for methyl at carbon 26. They were isolated from the culture broth of Streptomyces bottropensis NK86-0279. The structure of these two compounds was deduced by spectroscopic and X-ray crystallographic analyses. These antibiotics showed potent antitumor activities against various tumor cells in vitro, and were active against Colon 26 carcinoma in vivo. Although they showed no activity at 1,000 micrograms/ml against Gram-positive and Gram-negative bacteria and yeast, they have antifungal activity.