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

Fukuda, Takashi; Hirabayashi, Yoko; Hagimori, Keiichi; Yamaguchi, Yuichi; Masuma, Rokuro; Tomoda, Hiroshi; Ōmura, Satoshi

doi:10.1038/ja.2006.67

Cited by 22 publications

(14 citation statements)

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“…7 In this case, a 2008 report by Ding et al unknowingly provided structure 8 9 as a reasonable revision for compound 6 . Our evaluation of both data sets confirmed that the 1 H and 13 C NMR chemical shifts reported for the two compounds were identical and that 8 should be regarded as the correct structure of this metabolite.…”

Section: Resultsmentioning

confidence: 84%

“…Fortunately, the α -pyridone-containing variant had been previously examined by Ye and colleagues who successfully revised the proposed structure of aspernigrin A ( 3 ) 5 as the more plausible 2-benzylpyridin-4(1 H )-one shown for compound 4 . 8 Our analysis of the furopyrrol-containing molecules, which included tensidols A and B ( 5 - 6 ), 7 led to the observation that these structures had arisen from a strikingly different interpretation of 1 H and 13 C NMR data that were indistinguishable from the values reported for the 2-benzyl-4 H -pyran-4-ones carbonarone A ( 7 ) 6 and pestalamide A ( 8 ), 9 respectively. In this report, we address the structure revision of the tensidols using a combination of NMR spectroscopy, ab initio carbon chemical shift calculations, and total synthesis.…”

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confidence: 90%

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Reappraising the Structures and Distribution of Metabolites from Black Aspergilli Containing Uncommon 2-Benzyl-4H-pyran-4-one and 2-Benzylpyridin-4(1H)-one Systems

et al. 2011

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To date, natural products containing 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one substructures have been encountered in relatively few fungi outside of the black aspergilli clade. While exploring the occurrence of these compounds among Aspergillus spp., it was determined that the structures of the unusual furopyrrols tensidols A and B (5 and 6) and JBIR-86 and JBIR-87 (9 and 10) were incorrect and should be reassigned as 2-benzyl-4H-pyran-4-ones (7, 8, 11e, and 12, respectively). The origin of the unique N-phenyl groups in the 2-benzylpyridin-4(1H)-ones nygerones A and B (1 and 2) was also examined and it was established that N-phenylamides added to the culture medium were suitable substrates for generating these metabolites; however, this phenomenon remained limited to a single fungus in our collection (Aspergillus niger ATCC 1015). A variety of 2-benzyl-4H-pyran-4-ones and 2-benzylpyridin-4(1H)-ones were detected among the black aspergilli, but only pestalamide B (13) was found in all eleven of the tested strains. These metabolites, as well as a group of synthetic analogues demonstrated weak antifungal activity against several Candida strains, Aspergillus flavus, and Aspergillus fumigatus.

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Section: Resultsmentioning

confidence: 84%

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confidence: 90%

Reappraising the Structures and Distribution of Metabolites from Black Aspergilli Containing Uncommon 2-Benzyl-4H-pyran-4-one and 2-Benzylpyridin-4(1H)-one Systems

et al. 2011

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“…However, mixing two or more effective drugs with different mechanisms of action cannot guarantee an improved outcome compared with the results seen with a single agent. BEA was identified before as a potentiator of antifungal miconozole activity in vitro (38,39). Some nonantifungal compounds were also found to enhance the activity of conventional antifungal agents (40).…”

Section: Discussionmentioning

confidence: 99%

High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections

Zhang

Kou

Zhang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of Ϸ20,000 microbial extracts, 12 hits were identified with broadspectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.antifungal ͉ beauvericin ͉ ketoconazole

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“…On the basis of the new concept of "antiinfective drugs," 5) we have screened microbial metabolites for potentiators of miconazole activity against C. albicans. As a result, we discovered various new compounds: actofunicone, 6) beauvericins, 7) citridones, 8,9) tensidoles 10) and citrinamides 11) from fungi and phenatic acids 12) from an actinomycete. From precise analysis of the metabolites of xanthoradone-producing Penicillium radicum FKI-3765-2, 13) a new compound, designated 6Ј-hydroxy-3Ј-methoxy-mitorubrin (1, Fig.…”

Section: Regular Articlementioning

confidence: 99%

6'-Hydroxy-3'-methoxy-mitorubrin, a New Potentiator of Antifungal Miconazole Activity, Produced by Penicillium radicum FKI-3765-2

2010

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ExperimentalMicroorganisms P. radicum FKI-3765-2, previously reported as a xanthoradone-producing fungus, 13,14) was used for production of 1. The following seven microorganisms were used for antimicrobial tests: Bacillus subtilis ATCC 6633, Staphylococcus aureus FDA 209P, Micrococcus luteus PCI 1001, Escherichia coli NIHJ, Xanthomonas campestris pv. Oryzae KB 88, Mucor racemosus IFO 4581 and C. albicans KF-1.General Experimental Procedures SSC-ODS-7515-12 (Senshu Scientific Co., Tokyo, Japan) was used for octadecyl silyl (ODS) column chromatography. HPLC was carried out using the L-6200 system (Hitachi, Ltd., Tokyo, Japan). To determine the amounts of 1 to 3 in the culture broths, samples (ethyl acetate extracts) were dissolved in methanol and analyzed by the HP1100 system (Hewlett-Packard Co., Palo Alto, CA, U.S.A.) under the following conditions: column, Symmetry (2.1ϫ150 mm; Waters Corp., Milford, MA, U.S.A.); flow rate, 0.20 ml/min; mobile phase, a 20-min linear gradient from 30% CH 3 CN to 70% CH 3 CN containing 0.050% H 3 PO 4 ; detection, UV at 210 nm. Under these conditions, 1 to 3 were eluted with a retention time of 9.94, 10.6 and 12.0 min, respectively. UV spectra were recorded on a spectrophotometer (8453 UV-Visible spectrophotometer; Agilent Technologies Inc., Santa Clara, CA, U.S.A.). IR spectra were recorded on a Fourier transform infrared spectrometer (FT-710; Horiba, Ltd., Kyoto, Japan). Optical rotations were measured with a digital polarimeter (DIP-1000; JASCO, Tokyo, Japan). FAB-mass spectra were recorded on a mass spectrometer (JMS-DX300; JEOL, Tokyo, Japan), and HR-FAB-mass spectra were recorded on a mass spectrometer (JMS-AX505 HA; JEOL, Tokyo, Japan). Various NMR spectra were measured with a spectrometer (XL-400; Varian, Inc., Palo Alto, CA, U.S.A.).Fermentation P. radicum FKI-3765-2 was fermented according to the method similar to xanthoradone production described previously.13) Briefly, a slant culture of strain FKI-3765-2 grown on LCA (0.10% glycerol, 0.080% KH 2 PO 4 , 0.020% K 2 HPO 4 , 0.020% MgSO 4 · 7H 2 O, 0.020% KCl, 0.20% NaNO 3 , 0.020% yeast extract and 1.5% agar, adjusted to pH 6.0 before sterilization) was inoculated into a 50-ml tube containing 10 ml of the seed medium (2.0% glucose, 0.50% polypeptone, 0.050% MgSO 4 · 7H 2 O, 0.20% yeast extract, 0.10% KH 2 PO 4 and 0.10% agar, adjusted to pH 6.0 before sterilization). The tube was shaken reciprocally for 3 d at 27°C. A 1 ml portion of the seed culture was then inoculated into a 500-ml Erlenmeyer flask (IWAKI, Tokyo, Japan) containing the production medium (50 g Italian rice; Japan Europe Trading Co., Ltd., Tokyo, Japan). The production medium was prepared as follows; Italian rice (50 g) was soaked with water for 2 h, and then collected through a colander. Soaked rice was placed in a 500-ml Elenmeyer flask and sterilized by autoclaving. Fermentation was carried out at 27°C for 13 d under static conditions. Isolation of Mitorubrin CongenersThe 13-d-old whole culture (1000 g) was extracted with 2.0 l of acetone. After the a...

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

Cited by 22 publications

References 5 publications

Reappraising the Structures and Distribution of Metabolites from Black Aspergilli Containing Uncommon 2-Benzyl-4H-pyran-4-one and 2-Benzylpyridin-4(1H)-one Systems

Reappraising the Structures and Distribution of Metabolites from Black Aspergilli Containing Uncommon 2-Benzyl-4H-pyran-4-one and 2-Benzylpyridin-4(1H)-one Systems

High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections

6'-Hydroxy-3'-methoxy-mitorubrin, a New Potentiator of Antifungal Miconazole Activity, Produced by Penicillium radicum FKI-3765-2

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