Rokuro Masuma

Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase)

Enzymes in the mitochondrial respiratory chain are involved in various physiological events in addition to their essential role in the production of ATP by oxidative phosphorylation. The use of specific and potent inhibitors of complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c reductase), such as rotenone and antimycin, respectively, has allowed determination of the role of these enzymes in physiological processes. However, unlike complexes I, III, and IV (cytochrome c oxidase), there are few potent and specific inhibitors of complex II (succinate-ubiquinone reductase) that have been described. In this article, we report that atpenins potently and specifically inhibit the succinate-ubiquinone reductase activity of mitochondrial complex II. Therefore, atpenins may be useful tools for clarifying the biochemical and structural properties of complex II, as well as for determining its physiological roles in mammalian tissues.

Materials for the fungus flora of Japan (47)

Albophoma yamanashiensis isolated from a forest soil in Yamanashi Prefecture is described as a new genus belonging to Nectrioidaceae, Coelomycetes.

Selective and Potent in Vitro Antitrypanosomal Activities of Ten Microbial Metabolites

More than 400 compounds isolated from soil microorganisms, and catalogued in the antibiotic library of the Kitasato Institute for Life Sciences, were screened against African trypanosomes. Ten compounds were found to have selective and potent antitrypanosomal activity in vitro: aureothin, cellocidin, destomycin A, echinomycin, hedamycin, irumamycin, LL-Z 1272β, O-methylnanaomycin A, venturicidin A and virustomycin A. Results of the in vitro assays using the GUTat 3.1 strain of Trypanosomal brucei brucei and the STIB900 strain of T. b. rhodesiense are presented. Cytotoxicity was determined using a human MRC-5 cell line. This is the first report of antitrypanosomal activities of the 10 microbial metabolites listed above.

Effect of sea water concentration on hyphal growth and antimicrobial metabolite production in marine fungi

We studied the effect of sea water concentration in a culture medium on fungal growth and the production of antimicrobial metabolites. Most of the marine fungal isolates were identified as members of the same genera as terrestrial isolates, such asAspergillus andTrichoderma. Many of the marine fungi isolated grew more abundantly as the sea water concentration increased. The production of antimicrobial materials was improved as the sea water concentration increased. Even though the marine fungi were considered to be similar to fungi from terrestrial environments, from a mycological perspective, the two types have different physiological characteristics. The fungi from marine samples are useful microbial resources in the search for new bioactive compounds.

Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. I. Production, isolation and biological properties.

A series of new acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors termed terpendoles were isolated from the culture broth of a fungal strain FO-2546 which was proposed to belong to a new genus designated as Albophoma yamanashiensis. Among four structurally related terpendoles, terpendole C showed the most potent ACAT inhibitory activity with an IC50 value of 2.1 microM in an in vitro enzyme assay, followed by terpendoles D (IC50: 3.2 microM), A (15.1 microM) and B (26.8 microM). Evaluation of their ACAT inhibition in the cell assay using J774 macrophages indicated that terpendole D exhibited the highest specificity (cytotoxicity vs. ACAT inhibition) among microbial ACAT inhibitors we discovered so far.

In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A–C, produced by Penicillium sp. FKI-4410

In the course of screening for antimalarial agents, five tropolone compounds were isolated from the culture broth of Penicillium sp. FKI-4410. Two were known compounds, puberulic acid and stipitatic acid. Three were new analogs of puberulic acid, designated viticolins A–C. Among them, puberulic acid exhibited potent antimalarial inhibition, with IC50 values of 0.01 μg ml−1 against chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro. Furthermore, puberulic acid showed weak cytotoxicity against human MRC-5 cells, with an IC50 value of 57.2 μg ml−1. The compound also demonstrated a therapeutic effect in vivo, which compared well against the currently used antimalarial drugs, and thus shows promise as a leading candidate for development into a new antimalarial compound.

Tensidols, New Potentiators of Antifungal Miconazole Activity, Produced by Aspergillus niger FKI-2342

Two new furopyrrols, designated tensidols A and B, were isolated from the culture broth of Aspergillus niger FKI-2342 by solvent extraction, silica gel column chromatography and HPLC. Their structures were elucidated and shown to have the common skeleton of 6-benzyl-6H-furo[2,3-b]pyrrole. Tensidols A and B potentiated miconazole activity against Candida albicans. Tensidols also showed moderate antimicrobial activity only against Pyricularia oryzae.

Enhancement of metabolites productivity of Penicillium pinophilum FKI-5653, by co-culture with Trichoderma harzianum FKI-5655

In the course of discovering new metabolites from co-culture of Penicillium pinophilum FKI-5653 and Trichoderma harzianum FKI-5655, a new compound, designated secopenicillide C, and four known compounds, penicillide, MC-141, pestalasin A and stromemycin were isolated. The production of these compounds, except pestalasin A, was enhanced in co-culture to be two to six times higher than in pure culture of Penicillium pinophilum FKI-5653, which was the producer of these compounds.

Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. I. Taxonomy, fermentation, isolation and biological properties.

New phenylfuropyridinones and related compounds, designated citridones A, B, B′ and C, were isolated along with known CJ-16,173, from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. Citridones (75 µM) potentiate the miconazole activity against Candida albicans, decreasing the IC50 value of miconazole from 14.5 nM to 3.5∼6.3 nM.

Stemphones, Novel Potentiators of Imipenem Activity against Methicillin-resistant Staphylococcus aureus, Produced by Aspergillus sp. FKI-2136

A fungal strain FKI-2136 identified as genus Aspergillus was found to produce potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus (MRSA). Two new compounds designated stemphones B and C were isolated along with a structurally related known compound cochlioquinone D from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and preparative HPLC. These compounds have a common tetracyclic quinone skeleton. Stemphone C potentiated imipenem activity against the MRSA 512 fold by decreasing MIC value of imipenem from 16 µg/ml to 0.03 µg/ml.