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Biomedical subjects

K Otoguro

Publications and source records attributed to K Otoguro.

At least 19 recordsLinked to original sources
PubMed2001

Potent antimalarial activities of polyether antibiotic, X-206.

In the course of our screening program to discover antimalarial antibiotics, which are active against drug resistant Plasmodium falciparum in vitro and rodents infected with P. berghei in vivo, from the culture broth of microorganisms, we found a selective and potent active substance produced by an actinomycete strain K99-0413. It was identified as a known polyether antibiotic, X-206. We also compared the in vitro antimalarial activities and cytotoxicities of 12 known polyethers with X-206. Among them, X-206 showed the most selective and potent inhibitory effect against both drug resistant and sensitive strains of P. falciparum. Comparison of biological activities and ion-affinities of the above antibiotics suggests that monovalent cations play an important biological role for the intracellular growth of P. falciparum in parasitized erythrocytes. Moreover, X-206 showed potent in vivo antimalarial activity on the rodent model, though the therapeutic window was narrow compared with its selective toxicity in vitro. These observations are the first report of antimalarial activity of X-206.

Actinomycetales↗
PubMed2000

Synthetic conversion of ACAT inhibitor to acetylcholinesterase inhibitor.

Natural product acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor pyripyropene A was synthetically converted to acetylcholinesterase (AChE) inhibitor via heterolitic cleavage of the 2-pyrone ring, followed by gamma-acylation/cyclization with several aroyl chlorides. The 4-pyridyl analogue selectively showed AChE inhibitory activity (IC50 7.9 microM) and no ACAT inhibitory activity IC50 = >1000 microM.

Cholinesterase Inhibitors↗
PubMed2000

Arisugacins C and D, novel acetylcholinesterase inhibitors and their related novel metabolites produced by Penicilium sp. FO-4259-11.

The mutant of Penicillium sp. FO-4259, an arisugacins A and B producing strain, was found to produce a series of metabolites, designated arisugacins C, D, E, F, G and H, which were structurally related to arisugacins A and B. These compounds were isolated from the culture broth and the physico-chemical and biological properties were examined. The IC50 values of arisugacins C and D against acetylcholinesterase (AChE) were 2.5 microM and 3.5 microM, respectively. However arisugacins E, F, G and H did not inhibit AChE at 100 microM. Though they showed only weak or no activity against AChE compared with arisugacins A and B, they may be useful for the study of the structure-activity relationship.

Cholinesterase Inhibitors↗
PubMed1999

Heme-dependent radical generation: possible involvement in antimalarial action of non-peroxide microbial metabolites, nanaomycin A and radicicol.

Antimalarial screening was performed for microbial metabolites that simulate artemisinin in their mode of action, a potent antimalarial component of an herbal remedy with a characteristic peroxide structure. Nanaomycin A was identified in this screen as an antimalarial compound, together with radicicol and several other compounds already reported (J. Antibiotics 51: 153 approximately 160, 1998). Nanaomycin A inhibited in vitro growth of the human malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM. It was as potent as radicicol and about 1/10 as potent as artemisinin. Studies on the mode of action suggested that the antimalarial action of the two non-peroxides, nanaomycin A and radicicol, involved heme-dependent radical generation, as is for the peroxide artemisinin. Namely, the inhibition of in vitro growth of malaria parasite by nanaomycin A or radicicol was reversed by tocopherol, a radical scavenger added to the assay mixture. Secondly, in a reaction system established for radical detection, in which a test radical donor and beta-alanylhistidine as a radical recipient were incubated with and without hemin, the two compounds caused heme-dependent decreases of beta-alanylhistidine, as did artemisinin. Among the 14 microbial metabolites identified during this screening, a correlation was observed between antimalarial activity and heme-dependent radical generating activity.

Animals↗
PubMed1996

[Combination effect of vancomycin and cefpirome against methicillin-resistant Staphylococcus aureus in vitro--antimicrobial activities in postantibiotic phase].

The antimicrobial activities of vancomycin (VCM) or cefpirome (CPR) at sub- and above-MICs against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) during the postantibiotic phase (PAE-phase) induced by CPR or VCM were examined. Antimicrobial activities were determined growth suppression (post antibiotic sub-MIC effect: PA SME) at sub-MICs, and bactericidal activity at sub- and above-MICs. During the PAE-phase induced by VCM, growth suppression and bactericidal activity of CPR were enhanced at sub-MICs, compared with the non PAE-phase. On the other hand, during the PAE-phase induced by CPR, not only were growth suppression and bactericidal activity of VCM enhanced at sub-MICs, but bactericidal activity were enhanced at above-MICs compared with non PAE-phase. These suggest that enhancement of growth suppression and bactericidal activity during PAE-phase was a factor of combination effect of VCM and CPR against MRSA.

Anti-Bacterial Agents↗
PubMed1996

Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. I. Screening, taxonomy, fermentation, isolation and biological activity.

An in vitro screening method for selective acetylcholinesterase (AChE) inhibitors was established. Inhibitory activity of AChE and butyrylcholinesterase (BuChE) was measured and the culture broths of microorganisms that showed selective inhibition against AChE were characterized. By using this method, a strain producing the novel and selective inhibitors of AChE, arisugacins A and B, was picked out among over seven thousand microorganisms tested. Arisugacins were obtained as white powders from the culture broth together with three known compounds, territrems B and C and cyclopenin that also showed selective inhibition against AChE. Arisugacins and territrems are members of the meroterpenoid compounds. They showed potent inhibitory activities against AChE with IC50 values in range of 1.0 approximately 25.8 nM. Furthermore, they showed greater than 2,000-fold more potent inhibition against AChE than BuChE.

Cholinesterase Inhibitors↗
PubMed1996

Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. II. Structure elucidation.

The structures of new acetylcholinesterase inhibitors, arisugacins A and B, were elucidated by NMR study. Arisugacins have a (4aR,6aR,12aS,12bS)-4a,6,6a,12,12a, 12b-hexahydro-4a,12a-dihydroxy-4,4,6a,12b-tetramethyl-4H,11H -naphtho[2,1-b] pyrano[3,4-e]pyran-1,11(5H)-dione moiety in common and 3,4-dimethoxyphenyl or 4-methoxyphenyl residues are attached to C-9 of the moiety.

Cholinesterase Inhibitors↗
PubMed1993

A new antibiotic, cypemycin. Taxonomy, fermentation, isolation and biological characteristics.

A new peptide antibiotic, cypemycin, with a molecular weight of 2,097 (M+H), was isolated from the culture broth of Streptomyces sp. OH-4156. The antibiotic possesses cytocidal activity against P388 leukemia cells in vitro at a concentration of 1.3 microgram/ml (IC50 values), and the antibiotic showed antimicrobial activities against Micrococcus luteus (MIC, 0.2 microgram/ml).

Amino Acid Sequence↗
PubMed1991

Synthesis and nematocidal activities of jietacin A and its analogs.

Simple, efficient syntheses of jietacin A, a nematocidal antibiotic, and its analogs have been developed in order to study structure-activity relationships. A series of alpha,beta-unsaturated azoxy compounds was prepared from phenylselenomethyl azoxy compounds as key intermediates and its nematocidal activity was determined.

Animals↗