Novel antibiotics, furaquinocins A and B. Taxonomy, fermentation, isolation and physico-chemical and biological characteristics

Two novel antibiotics, furaquinocins A and B were isolated from the culture broth of Streptomyces sp. KO-3988. These antibiotics possess cytocidal activities against HeLa S3 cells in vitro at concentrations of 3.1 micrograms/ml for A and 1.6 micrograms/ml for B. Neither substance possessed antimicrobial activities against Gram-positive and Gram-negative bacteria, fungi or yeast at a concentration of 1,000 micrograms/ml.     

Sperabillins, new antibacterial antibiotics with potent in vivo activity. Taxonomy, fermentation, isolation and biological activity.

A Gram-negative bacterium was found to produce new antibacterial antibiotics, sperabillins A, B, C and D, and the producing bacterium was characterized and identified as Pseudomonas fluorescens YK-437. Sperabillins were isolated by column chromatographies using cation-exchange resins, activated carbon and cation-exchange Sephadex, and preparative reverse-phase HPLC. Sperabillins showed antibacterial activity against Gram-negative and Gram-positive bacteria including antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Sperabillin A inhibited DNA, RNA, protein, and cell wall biosynthesis in Escherichia coli. Sperabillins showed good protective effects in experimentally infected mice.     

Pyloricidins, novel anti-helicobacterpylori antibiotics produced by Bacillus sp. I. Taxonomy, fermentation and biological activity

Novel anti-Helicobacter pylori antibiotics, pyloricidins A, A1, A2, B, C and D, were discovered in the culture broth of two bacilli strains. Pyloricidins selectively inhibited the growth of H. pylori. Pyloricidin B was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils and may be promising for cure of H. pylori infection as a single agent.     

PD 116,152, a novel phenazine antitumor antibiotic. Discovery, fermentation, culture characterization and biological activity

A novel phenazine antitumor antibiotic is described, produced by Streptomyces lomondensis subsp. galanosa NRRL 15738. The antibiotic is selectively active versus the bacterium Streptococcus pneumoniae (MIC less than 0.46 microgram/ml); the antitumor activity versus murine P388 leukemia is T/C 149.     

Kedarcidin, a new chromoprotein antitumor antibiotic. I. Taxonomy of producing organism, fermentation and biological activity

Strain L585-6 (ATCC 53650) is an actinomycete isolated from a soil sample collected in Maharastra State, India. It produces a new chromoprotein antitumor antibiotic, designated kedarcidin. Taxonomic studies demonstrated that strain L585-6 is an unidentified and unknown actinomycete. Kedarcidin shows potent antitumor activity against implanted P388 leukemia (3.3 micrograms/ml/kg) and B16 melanoma (2 micrograms/kg) in mice. Kedarcidin also shows potent antimicrobial activity against Gram-positive bacteria but no activity against Gram-negative bacteria.     

Novel antifungal antibiotics octacosamicins A and B. I. Taxonomy, fermentation and isolation, physico-chemical properties and biological activities

Two antifungal antibiotics octacosamicins A and B were isolated from the culture broth of a strain of actinomycetes, which was identified as a strain of Amycolatopsis. These antibiotics were isolated by resin adsorption and purified by column chromatography and preparative HPLC. Both antibiotics were found to be new substances from their physico-chemical properties. They showed broad antifungal spectra.     

Kigamicins, novel antitumor antibiotics. I. Taxonomy, isolation, physico-chemical properties and biological activities

Novel antibiotics named kigamicin A, B, C, D, and E were discovered from the culture broth of Amycolatopsis sp. ML630-mF1 by their selective killing activity against PANC-1 cells only under a nutrient starved condition. Under a condition of nutrient starvation, kigamicins A, B, C, and D inhibited PANC-1 cell survival at 100 times lower concentration than in normal culture. Kigamicins showed antimicrobial activity against Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA). Kigamicin D inhibited the growth of various mouse tumor cell lines at IC50 of about 1 microg/ml.     

Thrazarine, a new antitumor antibiotic. I. Taxonomy, fermentation, isolation and biological properties

Thrazarine, O-[(3R)-2-diazo-3-hydroxybutyryl)]-L-serine, is a new antitumor antibiotic produced by Streptomyces coerulescens MH802-fF5. Thrazarine was isolated from culture filtrate by Sephadex LH-20 column chromatography and reversed phase HPLC. Thrazarine induced cytolysis of tumor cell lines co-cultured with nonactivated macrophages. This effect was tumor specific because the nontumorigenic cells were not lysed by macrophages in the presence of thrazarine. Thrazarine inhibited DNA synthesis and growth of tumor cells directly. It showed neither antimicrobial activity nor the inhibition of transamidation reactions in contrast to azaserine. Toxicities of thrazarine were much weaker than those of azaserine.     

Novel cytocidal antibiotics, glucopiericidinols A1 and A2. Taxonomy, fermentation, isolation, structure elucidation and biological characteristics

Two novel antibiotics, glucopiericidinols A1 (1) and A2 (2) were isolated from the cultured broth of Streptomyces sp. OM-5689. The structures of these two compounds were deduced employing spectroscopic analyses. These antibiotics showed potent cytocidal activities against HeLa S3 cells in vitro (MIC 1: 0.39 microgram/ml, 2: 0.10 microgram/ml) when the cells were exposed to the antibiotics for 3 days. Although 1 and 2 showed no activity at 1,000 micrograms/ml against various Gram-positive and Gram-negative bacteria, yeast or fungi, they did have inhibitory activity against Piricularia oryzae (MIC of 1: 125 micrograms/ml, of 2: 31 micrograms/ml).     

Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. I. Taxonomy of producing organism, fermentation and biological activity

Strain C39108-P210-51 (ATCC 53653), an actinomycete isolated from a soil sample collected in India, was found to produce a new antitumor antibiotic, designated himastatin. Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Streptomyces hygroscopicus C39108-P210-51. Himastatin shows antimicrobial activity against Gram-positive bacteria but it is inactive against Gram-negative bacteria. Himastatin prolongs the life span of mice inoculated with P388 leukemia and B16 melanoma cells.     

Aridicins, novel glycopeptide antibiotics. I. Taxonomy, production and biological activity

A new species of a new genus of the Actinomycetales was discovered, Kibdelosporangium aridum. This strain produces a new family of glycopeptide antibiotics designated aridicins, that contain an unusual glycolipid constituent. They inhibit Gram-positive bacteria, including staphylococci, enterococci and Clostridium sp.     

PD 124,895 and PD 124,966, two new antitumor antibiotics

The isolation and characterization of the title antibiotics, which are produced by the same Streptomyces sp., is described. The potent antitumor agent, PD 124,895, is an analog of hydroxyelactocin (PD 114,721). PD 124,966 is a new member of the depsipeptide family of antibiotics.     

Yaequinolones, new insecticidal antibiotics produced by Penicillium sp. FKI-2140. I. Taxonomy, fermentation, isolation and biological activity

New nine insecticidal antibiotics designated yaequinolones were isolated from the culture broth of the fungal strain Penicillium sp. FKI-2140 by solvent extraction, centrifugal partition chromatography and HPLC. Yaequinolones showed growth inhibitory activity against brine shrimp (Artemia salina). Among them, yaequinolone F has the most potent activity with MIC value of 0.19 microg/ml.     

Resorthiomycin, a novel antitumor antibiotic. I. Taxonomy, isolation and biological activity

Resorthiomycin, a novel antitumor antibiotic, was isolated from the fermentation broth of a strain of Streptomyces collinus by ethyl acetate extraction, silica gel chromatography and HPLC. Resorthiomycin exhibited an in vitro cytotoxic activity against mouse leukemia L5178Y cells (IC50, 15.5 micrograms/ml) and also inhibited the clonogenic activity of a multidrug-resistant mutant of human hepatoma PLC/PRF/5 cells to a greater extent than that of the parental cells. On the other hand, this antibiotic does not possess any antibacterial or antifungal activity.     

APHE-1 and APHE-2, two new antimicrobial and cytotoxic antibiotics. I. Taxonomy, fermentation, isolation and biological activity.

APHE-1 and APHE-2 are two new antibiotics produced by Streptoverticillium griseocarneum NCIMB 40447. They exhibited a remarkable cytotoxic activity against several tumor cell lines from different origin. Furthermore, they showed weak antimicrobial activity against Gram-positive bacteria, filamentous fungi and yeasts.     

Novel antifungal antibiotics maniwamycins A and B. I. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological properties

Two antifungal antibiotics maniwamycins A and B were isolated from the culture broth of a strain of actinomycetes, which were classified as Streptomyces prasinopilosus. These antibiotics were isolated by resin absorption and extraction with EtOAc and purified by column chromatography. Both antibiotics were found to be new azoxy substances from their physico-chemical properties. They showed broad antifungal spectra.     

Formadicins, new monocyclic beta-lactam antibiotics of bacterial origin. I. Taxonomy, fermentation and biological activities

A Gram-negative bacterium produces new monocyclic beta-lactam antibiotics with a formylamino substituent, named formadicins A, B, C and D. The producing bacterium was taxonomically characterized and designated as Flexibacter alginoliquefaciens sp. nov. YK-49. Formadicins have narrow antibacterial spectra. They are highly active against some species of Pseudomonas, Proteus and Alcaligenes. Of the four, formadicin C shows the most potent antibacterial activity. Several amino acids such as glycine, D-alanine and D-leucine were antagonistic against formadicins. Formadicins, especially formadicins A and C having the formylamino substituent bound to the 3-position of a beta-lactam nucleus, were highly resistant to hydrolysis by various types of beta-lactamases. Formadicins A and C showed affinity for penicillin-binding proteins (PBPs) 1A and 1B in Pseudomonas aeruginosa IFO 3080, but formadicin B and nocardicin A showed affinity only for PBP 1B. Formadicins A and C did not lyse Escherichia coli LD-2 solely at their MICs, but when combined with mecillinam each induced a rapid lysis of this organism.     

Nocathiacins,new thiazolyl peptide antibiotics from Nocardia sp. I. Taxonomy,fermentation and biological activities

Thiazolyl peptide antibiotics, nocathiacin I, II and III, were identified in a culture of Nocardia sp. WW-12651 (ATCC 202099). They exhibit potent in vitro activity (ng/ml) against a wide spectrum of gram-positive bacteria, including multiple-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Enterococcus faecium (MREF) and fully penicillin-resistant Streptococcus pneumoniae (PRSP), and demonstrate excellent in vivo efficacy in a systemic Staphylococcus aureus infection mice model.     

Arizonins, a new complex of antibiotics related to kalafungin. I. Taxonomy of the producing culture, fermentation and biological activity

The arizonins, a novel complex of antibiotics related to kalafungin, were discovered in the fermentation broth of Actinoplanes sp. AB660D-122. Comparative taxonomic studies indicated that the culture is a new species and therefore has been designated Actinoplanes arizonaensis sp. nov. Two members of the complex, arizonins A1 and B1, exhibit moderate to potent in vitro antimicrobial activity against pathogenic strains of Gram-positive bacteria.     

Butalactin, a new butanolide antibiotic. Taxonomy, fermentation, isolation and biological activity

Butalactin, [2-(4',5'-epoxy-hex-2'(E)-en)oyl-2-hydroxy-3-hydroxymethyl-2, 3-(Z)-butanolide] is a new antibiotic produced by Streptomyces sp. HIL Y-86,36923. Taxonomically, the producing organism most closely resembles Streptomyces corchorusii. The strain also produces cineromycin B. Though butalactin is structurally related to 'signal molecules' such as A-factor, the anthracycline inducing factors and the virginiae butanolides, it does not show inducing activity for antibiotic production or aerial mycelium formation in the indicator strain. Butalactin possesses a weak antibiotic activity against Gram-positive and Gram-negative bacteria.