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Biomedical subjects

M Namikoshi

Publications and source records attributed to M Namikoshi.

At least 37 records · Page 2Linked to original sources
PubMed1993

Structural modifications imparting reduced toxicity in microcystins from Microcystis spp.

A cyanobacterial (blue-green algal) bloom containing Microcystis aeruginosa (dominant), M. viridis, and M. wesenbergii, was collected from Homer Lake (Illinois, U.S.A.) in the summer of 1988 and microcystins were isolated. One microcystin of substantially reduced toxicity was isolated, together with ten hepatotoxic microcystins. The compound with reduced toxicity was nonlethal at 1 mg/kg (i.p. mouse) and was determined to have a (C3H7O2) mono-ester of the alpha-carboxyl on the Glu unit of microcystin-LR. The other nine microcystins apart from MCLR had approximate LD50S ranging from 97 micrograms/kg to 750 micrograms/kg.

Amino Acid Sequence↗
PubMed1993

Isolation and identification of eight microcystins from thirteen Oscillatoria agardhii strains and structure of a new microcystin.

Microcystins (cyclic heptapeptide hepatotoxins), isolated from 13 freshwater Oscillatoria agardhii strains from eight different Finnish lakes by high-performance liquid chromatography, were characterized by amino acid analysis, fast atom bombardment mass spectrometry (FABMS), and tandem FABMS (FABMS/collisionary-induced dissociation/MS). All strains produced two to five different microcystins. In total, eight different compounds, of which five were known microcystins, were isolated. The known compounds identified were [D-Asp3]MCYST (microcystin)-LR, [Dha7]MCYST-LR, [D-Asp3]MCYST-RR, [Dha7]MCYST-RR, and [D-Asp3,Dha7]MCYST-RR. This is the first time that isolation of these toxins from Oscillatoria spp., with the exception of [D-Asp3]MCYST-RR, has been reported. Three of the strains produced a new microcystin, and the structure was assigned as [D-Asp3,Mser7]MCYST-RR. The structures of two new microcystins, produced as minor components by one Oscillatoria strain, could not be determined because of the small amounts isolated from the cells. Four strains produced [Dha7]MCYST-RR as the main toxin, but [D-Asp3]MCYST-RR was clearly the most abundant and most frequently occurring toxin among these isolates of O. agardhii.

Amino Acid Sequence↗
PubMed1993

Clinical and pathologic findings of blue-green algae (Microcystis aeruginosa) intoxication in a dog.

A healthy dog developed signs of lethargy and vomiting after ingesting water from a tide pool containing blue-green algae. Fulminant hepatic failure occurred, and the dog was euthanized 52 hours later. At necropsy, the liver was large, friable, and discolored a dark red. Histopathology showed hepatocyte dissociation, degeneration, and necrosis. The alga was identified as Microcystis aeruginosa, a known hepatotoxin. The intraperitoneal administration of lyophilized cell material from the bloom caused hepatic necrosis in mice.

Animals↗
PubMed1993

Chemical study of the hepatotoxins from Microcystis aeruginosa collected in California.

Four cyclic peptide toxins were purified and quantified from the aqueous extract of algal cell material utilizing high performance liquid chromatography, thin layer chromatography, and fast atom bombardment mass spectrometry. The cyclic peptide toxins appear to be similar structurally to hepatotoxins from previously identified blooms of the blue-green alga Microcystis aeruginosa.

Amino Acid Sequence↗
PubMed1992

Structure determination and toxicity of a new microcystin from Microcystis aeruginosa strain 205.

A new hepatotoxic microcystin was isolated from the cyanobacterium Microcystis aeruginosa strain 205. Its structure was found to be [Dha7]microcystin-RR as determined by amino acid analysis, mass spectrometry and 1H NMR spectroscopy. LD50 value (i.p. mouse) of this toxin was 180 micrograms/kg. The 48 hr lethal concentration (48-hr-LC50) of the toxin for larvae of the yellow fever mosquito, Aedes aegypti, was 14.9 micrograms/ml.

Aedes↗
PubMed1992

Two new L-serine variants of microcystins-LR and -RR from Anabaena sp. strains 202 A1 and 202 A2.

Two new microcystins, [L-Ser7]microcystin-LR (1) and [L-Ser7]microcystin-RR (2), were isolated from a filamentous fresh water cyanobacterium (blue-green alga), Anabaena sp. strain 202 A1, along with the two major toxins, [Dha7]microcystin-LR (3) and [Dha7]microcystin-RR (4) and their minor components the D-Asp variants [D-Asp3,Dha7]microcystin-LR (5) and [D-Asp3,Dha7]microcystin-RR (6). Anabaena sp. strain 202 A1 also produced another new toxin, whose structure is tentatively proposed as [D-Asp3,L-Ser7]microcystin-XR (7), where X is a leucine homologue. Anabaena sp. strain 202 A2 produced one new microcystin, 1, and three known microcystins, 3, 4, and 5. The structures of the toxins were assigned based on their amino acid analyses, and fast atom bombardment mass spectrometry data.

Amino Acid Sequence↗
PubMed1992

Two methyl ester derivatives of microcystins, cyclic heptapeptide hepatotoxins, isolated from Anabaena flos-aquae strain CYA 83/1.

Cultured cells of Anabaena flos-aquae strain CYA 83/1, isolated from Lake Edlandsvatn, Norway, produced two microcystin mono-methyl ester derivatives (1 and 2) at the D-Glu unit in addition to microcystin-LR (3), [D-Asp3]microcystin-LR (4), microcystin-RR (5), and [D-Asp3]microcystin-RR (6). Structures of these compounds were assigned based on their amino acid analysis with a Waters Pico Tag HPLC system plus fast atom bombardment mass spectrometry (FABMS), including tandem FABMS, analysis on the two new microcystins, [D-Glu(OCH3)6]microcystin-LR (1) and [D-Asp3, D-Glu(OCH3)6]microcystin-LR (2). Toxicity data were not obtained for 1 and 2 because of the small amounts isolated from the cells.

Amino Acid Sequence↗
PubMed1992

Isolation and structures of microcystins from a cyanobacterial water bloom (Finland).

A hepatotoxic cyanobacterial (blue-green algal) water bloom was collected from a constructed water reservoir in Finland. The water bloom contained two cyanobacterial species, Microcystis aeruginosa and Aphanizomenon flos-aquae. Two hepatotoxins, 1 and 2, were isolated from extracts of lyophilized cells. The structures of 1 and 2 were assigned based upon their amino acid analyses on a Waters Pico Tag HPLC system and a chiral GC capillary column (Chirasil Val III), fast atom bombardment mass spectrometry (FABMS), high resolution FABMS, and tandem FABMS data. Toxin 1 was identical to a previously reported compound, [D-Asp3]microcystin-RR. Toxin 2 was new and was assigned the structure [D-Asp3]microcystin-YR.

Amino Acids↗
PubMed1992

Isolation and structures of five microcystins from a Russian Microcystis aeruginosa strain CALU 972.

Five microcystins were obtained from Microcystis aeruginosa strain CALU 972 isolated from a hepatotoxic water bloom collected in Lake Kroshnosero (Russia). The structure of a new toxin (1) was determined as [Dha7]microcystin-YR by amino acid analyses and fast atom bombardment mass spectrometry, and the toxins 2, 3, 4, and 5 were assigned the structures as [Dha7]microcystin-LR, [D-Asp3,Dha7]microcystin-LR, [Dha7]microcystin-RR, and [D-Asp3,Dha7]microcystin-RR, respectively, by direct comparison with authentic samples.

Amino Acid Sequence↗
PubMed1992

Isolation and characterization of a variety of microcystins from seven strains of the cyanobacterial genus Anabaena.

Hepatotoxins (microcystins) from seven freshwater Anabaena strains originating from three different Finnish lakes and one lake in Norway were isolated by high-performance liquid chromatography and characterized by amino acid analysis and fast atom bombardment mass spectrometry. All strains produced three to seven different microcystins. A total of 17 different compounds were isolated, of which 8 were known microcystins. The known compounds identified from six strains were MCYST (microcystin)-LR, [D-Asp3]MCYST-LR, [Dha7]MCYST-LR, [D-Asp3,Dha7]MCYST-LR, MCYST-RR, [D-Asp3]MCYST-RR, [Dha7]MCYST-RR, and [D-Asp3,Dha7]MCYST-RR. With the exception of MCYST-LR and [D-Asp3]MCYST-LR, this is the first time that isolation of these toxins from Anabaena strains has been reported. Three of the strains produced one to three toxins as minor components which could not be identified. Anabaena sp. strain 66 produced four unidentified toxins. The other Anabaena strains always contained both MCYST-LR and MCYST-RR and/or their demethyl variants. Quantitative differences between toxins within and between strains were detected; at times MCYST-LR and at other times MCYST-RR or demethyl derivatives thereof were the most abundant toxins found in a strain.

Amino Acid Sequence↗
PubMed1990

Isolation and characterization of hepatotoxic microcystin homologs from the filamentous freshwater cyanobacterium Nostoc sp. strain 152.

A strain of the filamentous cyanobacterium Nostoc sp. isolated from a lake in Finland was found to produce at least nine hepatotoxic peptides with chemical and toxicological properties similar to those of the hepatotoxic hepta- and pentapeptides produced by other cyanobacteria. Toxins were isolated and purified by high-performance liquid chromatography. Amounts available for five of the purified toxins (P6, P14, P15, P16, and P18) were adequate for high-performance liquid chromatography amino acid analysis and determination of molecular weight by fast-atom bombardment-mass spectrometry (FAB-MS). Quantities of three toxins (P14, P15, and P16) were adequate for further analysis by high-resolution FAB-MS, FAB-MS/MS, and 1H-nuclear magnetic resonance. Analysis showed that the toxins are new types of microcystin-LR homologs. Microcystin-LR contains equimolar amounts of D-alanine, L-leucine, D-erythro-beta-methylaspartic acid, L-arginine, ADDA (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid), D-glutamic acid, and N-methyldehydroalanine (molecular weight [MW], 994). Nostoc sp. strain 152 was found to produce the following microcystin-LR homologs: (i) P6 contains an extra methylene group most probably due to the presence of N-methyldehydrobutyrine instead of N-methyldehydroalanine (MW, 1,008); (ii) P14 is O-acetyl-O-demethyl ADDA-microcystin-LR (MW, 1,022); (iii) P15 is 3-demethyl-O-acetylADDA-homoarginine-microcystin-LR (MW, 1,036); (iv) P16 is 3-demethyl-O-acetyl-O-demethylADDA-microcystin-LR (MW, 1,008); (v) P18 is 3-demethyl-O-acetyl-O-demethylADDA-homoarginine-microcystin- LR (MW, 1,022). The toxicities of the new microcystin homologs were not significantly different from those of microcystin-LR or demethylmicrocystin-LR.

Amino Acids↗
PubMed1986

Studies on macrocyclic lactone antibiotics. VIII. Absolute structures of rhizoxin and a related compound.

The absolute structure of rhizoxin, a potent antifungal and antitumor antibiotic, was determined by interrelation with compound 2 whose structure was established by X-ray analysis. Since a 18OH group was introduced at C-3 on a hydrolytic cleavage of C-2, C-3 epoxy group with alkaline H2(18)O, the original epoxy oxygen should be retained at C-2. The stereo-chemistry at C-2 and C-3 positions in rhizoxin was, therefore, determined as 2R,3S.

Chemical Phenomena↗
PubMed1985

Biosynthetic studies on saframycin A, a quinone antitumor antibiotic produced by Streptomyces lavendulae.

The biosynthesis of saframycin A, a heterocyclic quinone antitumor antibiotic isolated from Streptomyces lavendulae 314, was studied by feeding experiments with 14C and 13C precursors. Highly increased production of saframycin A and prolongation of the maximum production period of saframycin A were attained by constant pH control of the culture and by addition of chloramphenicol to the culture. The biosynthetic origin of the quinone skeleton common to the saframycin group was confirmed to be two tyrosine molecules which condense to generate the basic ring system of saframycin A. Feeding experiments with [1-13C]tyrosine showed specific labeling of C-11 and C-21 carbons of saframycin A, and the enrichment of the carbons was 40-fold over natural abundance. Two O- and two C-methyl and one N-methyl carbons arose directly from methionine, and alanine and glycine were the precursors for the pyruvoyl amide side chain of saframycin A.

Amino Acids↗
PubMed1984

Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis.

A new 16-membered macrolide designated as rhizoxin was isolated as a toxin produced by Rhizopus chinensis, the causal agent of rice seedling blight . The skeletal structure was determined by detailed NMR spectroscopic investigation of this compound and of its derivatives. Rhizoxin induced at a concentration of 10 ng/ml abnormal swelling of rice seedling roots, which is one of the characteristic symptoms of this disease. This compound also exhibited potent antifungal activity but little effect against bacteria.

Anthraquinones↗
PubMed1982

Studies on macrocyclic lactone antibiotics. VI. Skeletal structure of copiamycin.

Skeletal structure of copiamycin (1) (C54H95N3O17), a potent antifungal antibiotic, was determined from the physicochemical properties of this compound and of its degradation products. This compound consists of 32-membered polyhydroxy lactone ring, an alpha, beta-unsaturated ester group, as well as a side chain with a disubstituted guanidine moiety as its terminal. One of the hydroxyl groups (presumably at C-19) forms a hemiketal ring with the keto group at C-15, and another (at either C-21 or C-23) forms a hemiester with a malonic acid moiety.

Anti-Bacterial Agents↗
PubMed1982

Cadeguomycin, a novel nucleoside analog antibiotic. II. Improved purification, physicochemical properties and structure assessment.

Cadeguomycin, a new nucleoside analog antibiotic, has been purified as colorless needle crystals by recycling preparative HPLC. The antibiotic, C12H14O7N4, mp 231 approximately 239 degrees C (dec.), FD-MS: m/z 326 (M+); is a weakly acidic substance, showing UV gamma H2Omax (epsilon) 232 (19677), 272 (6881) and 298 nm (7607), and IR nu KBrmax 1650 (C = O) and 3420 (NH or OH) cm-1. The UV spectrum is similar to other pyrrolo[2,3-d]pyrimidines. The structure of cadeguomycin, 2-amino-3,4-dihydro-4-oxo-7-beta-D-ribofuranosyl-7H-pyrrolo[2,3-d]pyrimidine-5- carboxylic acid, has been elucidated by 1H NMR and 13C NMR in comparison with other pyrrolo[2,3-d]pyrimidines and their nucleosides.

Anti-Bacterial Agents↗
PubMedDate not supplied

Three new microcystins, cyclic heptapeptide hepatotoxins, from Nostoc sp. strain 152.

Three new cyclic heptapeptide hepatotoxins, [D-Ser1,ADMAdda5]microcystin-LR (1), [D-Asp3,-ADMAdda5]microcystin-LHar (2), and [ADMAdda5,Mser7]microcystin-LR (3), were isolated from the cyanobacterium (blue-green alga) Nostoc sp. strain 152, together with four known microcystins, [ADMAdda5]microcystin-LR (4), [ADMAdda5]microcystin-LHar (5), [D-Asp3,-ADMAdda5]microcystin-LR (6), and [DMAdda5]microcystin-LR (7). The structures of new microcystins were assigned on the basis of high-resolution fast atom bombardment mass spectrometry (HR FABMS), collisionally induced tandem FABMS (FABMS/MS), amino acid analysis, and gas chromatography (GC) on a chiral capillary column. All three new toxins contained 9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (ADMAdda) instead of the corresponding 9-methoxyl derivative (Adda), while 7 contains the corresponding 9-hydroxy analog (DMAdda). Compound 1 is the first microcystin reported that contains D-serine (D-Ser) in lieu of the D-alanine (D-Ala) unit which was thought to be an invariable amino acid component of the microcystins. Compound 2 has L-homoarginine (Har) instead of L-arginine (L-Arg) in 6 and D-aspartic acid (D-Asp) instead of D-erythro-beta-methylaspartic acid (D-MeAsp) in 5. Compound 3, the N-methylserine (Mser) variant of the N-methyldehydroalanine unit in 4, would be a biosynthetic precursor of 4.

Amino Acids↗