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S K Tanaka

Publications and source records attributed to S K Tanaka.

30 records · Page 2Linked to original sources
PubMed1994

In vitro and in vivo evaluations of A-80556, a new fluoroquinolone.

A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC for 90% of isolates [MIC90], 0.12 microgram/ml, relative to fluoroquinolone-susceptible strains) and Streptococcus pneumoniae (MIC90, 0.12 microgram/ml). A-80556 was also the most active of the quinolones tested against ciprofloxacin-resistant S. aureus, with an MIC90 of 4.0 micrograms/ml; that of ciprofloxacin was > 128 micrograms/ml. However, the significance of this activity is not known. A-80556 was slightly less active against Escherichia coli (MIC90, 0.06 microgram/ml) and other enteric organisms than ciprofloxacin (MIC90 for E. coli, < or = 0.03 microgram/ml). A-80556 was slightly less active against Pseudomonas aeruginosa (MIC90, 4.0 micrograms/ml) than ciprofloxacin (MIC90, 2.0 micrograms/ml) and more active against Acinetobacter spp. (respective MIC90s, 0.12 and 0.5 microgram/ml). A-80556 was also the most active compound against anaerobes. Against Bacteroides fragilis, the MIC90 of A-80556 was 2.0 micrograms/ml; that of ciprofloxacin was 16 micrograms/ml. The in vivo efficacy of A-80556 in experimental models with both gram-positive and gram-negative infections was consistent with the in vitro activity and pharmacokinetics and oral absorption in mice.

Animals↗
PubMed1994

Synthesis and antitumour activities of tetracyclic quinolone antineoplastic agents.

DNA topoisomerases, found in all prokaryotic and eukaryotic cells, play a key role in controlling the topological state of DNA. They are involved in DNA replication, RNA transcription and recombination affecting cell proliferation. Quinolone antibacterial agents have been shown to be inhibitors of DNA gyrase, a bacterial topoisomerase II enzyme. The eukaryotic topoisomerase II is the target of various cytotoxic agents such as adriamycin and etoposide. Due to the mechanistic similarities and sequence homologies shared by both bacterial and mammalian DNA topoisomerase II, we initiated a screening programme to search for quinolones as antitumour agents and reported the identification of a new class of quinolone, quinobenoxazines, having excellent in vitro cytotoxic activity comparable to adriamycin. In the continuation of this research work, we synthesized a series of amino-substituted quinobenoxazines and found that some of them possess more potent in vitro cytotoxicity than the parent unsubstituted quinobenoxazines. The chemical synthesis as well as biological properties of these tetracyclic quinolones are described.

Animals↗
PubMed1993

Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity.

A novel antibiotic complex, named the calbistrins, has been discovered in the culture broth of a soil fungus. The producing organism, designated AB 1875C-28, was identified as a strain of Penicillium restrictum. Calbistrin A, the most potent of the 4-membered complex, has MICs of 0.78 micrograms/ml against Candida albicans. Only poor activity is observed against non-candida yeasts, filamentous fungi and bacteria.

Animals↗
PubMed1988

Inactivation of beta-lactamases from Enterobacter cloacae by monophosphams.

Amongst the monocyclic beta-lactam antibiotics, selected monophosphams were potent mechanism-based inactivators of the P99 and E2 cephalosporinases of Enterobacter cloacae. Inhibition of these enzymes was time-dependent with second order rate constants for inactivation of 100,000 to 20,000,000 l/mol/min. After incubation for 24 h at least 99% of the enzymatic activity was inhibited when enzyme was exposed to a ten-fold excess of inactivator. Amongst the monophosphams three classes of inhibitors were seen: irreversible inactivators as described above, transient inactivators and competitive (inhibitory) substrates.

Anti-Bacterial Agents↗
PubMed1988

Lysobactin, a novel antibacterial agent produced by Lysobacter sp. II. Biological properties.

Lysobactin, an antibiotic isolated from a strain of Lysobacter, is 2 to 4-fold more active than vancomycin against aerobic and anaerobic Gram-positive bacteria. Included in the spectrum of lysobactin are Staphylococci, Streptococci, corynebacteria, clostridia and various other Gram-positive anaerobic bacteria. The activity of lysobactin against aerobic and anaerobic Gram-negative bacteria is poor. When given parenterally the compound was efficacious in systemic staphylococcal and streptococcal infections in mice. Similarly, when applied topically lysobactin was also curative in a staphylococcal wound infection in mice. Some studies on the mode of action of lysobactin are presented.

Animals↗
PubMed1987

In vitro evaluation of tigemonam, a novel oral monobactam.

Tigemonam, a novel, orally administered monobactam, exhibited potent and specific activity in vitro against members of the family Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae. Its activity was variable to poor against gram-positive bacteria, Acinetobacter spp., Pseudomonas aeruginosa, and anaerobes. Within its spectrum of activity, tigemonam was far superior to oral antibiotics currently available, including amoxicillin-clavulanic acid, cefaclor, and trimethoprim-sulfamethoxazole. In addition, tigemonam was superior to cefuroxime, which is under development as an oral pro-drug, and more active than cefixime against several genera of the Enterobacteriaceae. The activity of tigemonam against the enteric bacteria, Haemophilus species, and Neisseria species was, in general, comparable to that of the quinolone norfloxacin. The excellent activity of tigemonam against beta-lactamase-producing bacteria reflected its marked stability to hydrolysis by isolated enzymes. The expanded spectrum of activity against gram-negative bacteria observed with tigemonam thus extends oral beta-lactam coverage to include members of the Enterobacteriaceae that are intrinsically or enzymatically resistant to broad-spectrum penicillins and cephalosporins.

Acinetobacter↗
PubMed1987

Improved sensitivity in assays for binding of novel beta-lactam antibiotics to penicillin-binding proteins of Escherichia coli.

Tigemonam and temocillin, but not aztreonam, bound to penicillin-binding proteins (PBPs) 1a and 3 of Escherichia coli with apparent improved affinity when challenged with benzylpenicillin at lowered temperatures. Half times for deacylation of the tigemonam-PBP complexes were shorter than were those of the corresponding aztreonam-PBP complexes. The implications of the routine testing of PBP affinities are discussed.

Anti-Bacterial Agents↗
PubMed1987

Xylocandin: a new complex of antifungal peptides. I. Taxonomy, isolation and biological activity.

Xylocandin is a complex of novel peptides with potent antifungal activity that is produced by Pseudomonas cepacia ATCC 39277. The complex was isolated from the fermentation broth by extraction with butanol-methanol, 9:1, followed by collection of the precipitate formed upon concentration of the solvent extract. Purification was effected by chromatography on reversed phase and size exclusion gels followed by TLC on silica gel. These techniques afforded eight components: A1, A2, B1, B2, C1, C2, D1 and D2. A mixture of the two closely related components, xylocandins A1 and A2, displayed potent anticandidal and antidermatophytic activities in vitro. The activity was diminished by the presence of serum or vaginal washings. No antibacterial activity was demonstrable.

Animals↗
PubMed1985

Resistance caused by decreased penetration of beta-lactam antibiotics into Enterobacter cloacae.

Strains of Enterobacter cloacae were selected on the basis of resistance to aztreonam, ceftazidime, moxalactam, or imipenem. All strains produced the same E2 beta-lactamase, with an isoelectric point greater than 9.5 and with high hydrolytic activity in the presence of cephaloridine. Resistance to beta-lactams could not be correlated with the amount of beta-lactamase present in the various strains. beta-Lactamase activity was induced strongly by moxalactam and imipenem in the wild-type and moxalactam-resistant strains, with beta-lactamase representing as much as 4% of the total cellular protein after induction (2 X 10(5) molecules per cell). Ceftazidime and aztreonam were poor inducers. None of the antibiotics studied was readily hydrolyzed by the E2 beta-lactamase; aztreonam and moxalactam inhibited the enzyme with apparent Ki values of 1.2 and 100 nM, respectively. Aztreonam, which bound covalently to the E2 beta-lactamase with a half-life of 2.3 h at 25 degrees C, was used to measure penetrability of beta-lactam into the periplasmic space of the resistant E. cloacae strains. In all of the E2-producing organisms studied, a significant permeability barrier existed. A maximum concentration of 0.02 microgram of aztreonam per ml should have saturated the periplasmic beta-lactamase in the highest enzyme producers studied. However, fully active beta-lactamase was observed in the periplasm of cells exposed to aztreonam at concentrations at least 1,000-fold higher than that theoretically necessary to inhibit the total enzyme within the cell. Thus, the major cause for resistance to beta-lactam antibiotics in these E. cloacae strains was lack of penetration across the outer membrane.

Anti-Bacterial Agents↗