Alutenusin, a Specific Neutral Sphingomyelinase Inhibitor, Produced by Penicillium sp. FO-7436.

Uchida, Ryuji; Tomoda, Hiroshi; Dong, Y.H.; Ōmura, Satoshi

doi:10.7164/antibiotics.52.572

Cited by 64 publications

(30 citation statements)

References 7 publications

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“…Altenusin was originally isolated from Alternaria tenuis [43] and subsequently isolated from various organisms, including Penicillium sp. [64]. It has been reported as a weak inhibitor of myosin light chain kinase (IC 50 =340 lM) [31], and sphingomyelinase (IC 50 =28 lM) [64].…”

Section: -O-methylanthrogallolmentioning

confidence: 97%

Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites

Singh

Jayasuriya

Dewey

et al. 2003

Journal of Industrial Microbiology and Biotechnology

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HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition is one of the most promising new drug strategies for anti-retroviral therapy, with potentially significant advantages over existing therapies. In this report, a series of HIV-1 inhibitors isolated from the organic extract of fermentations from terrestrial fungi is described. These fungal species, belonging to a variety of genera, were collected from throughout the world following the strict guidelines of Rio Convention on Biodiversity. The polyketide- and terpenoid-derived inhibitors are represented by two naphthoquinones, a biphenyl and two triphenyls, a benzophenone, four aromatics with or without catechol units, a linear aliphatic terpenoid, a diterpenoid, and a sesterterpenoid. These compounds inhibited the coupled and strand-transfer reaction of HIV-1 integrase with an IC(50) value of 0.5-120 micro M. The bioassay-directed isolation, structure elucidation, and HIV-1 inhibitory activity of these compounds are described.

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Section: -O-methylanthrogallolmentioning

confidence: 97%

Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites

Singh

Jayasuriya

Dewey

et al. 2003

Journal of Industrial Microbiology and Biotechnology

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“…Among the pharmacological inhibitors scyphostatin, obtained from mycelial extracts from the discomycete Trichopeziza mollissima, is becoming widely accepted as a neutral sphingomyelinase inhibitor [47,52,[103][104][105]. Other natural inhibitors of mammalian nSMase include macquarimicin A [106], alutenusin [107], chlorogentisylquinone [108], and manumycin A [109]. Some synthetic substrate analogues can also be used as SMase inhibitors [110][111][112].…”

Section: Sphingomyelinase Inhibitorsmentioning

confidence: 99%

Sphingomyelinases and Their Interaction with Membrane Lipids

Goñi

Alonso

2004

Lipases and Phospholipases in Drug Development

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This chapter is devoted to sphingomyelinases, enzymes that catalyze the hydrolysis of sphingomyelin (ceramide phosphorylcholine) into ceramide and phosphorylcholine. The reaction is formally similar to that of a phospholipase C. Sphingomyelinases have long been known [1, 2], but the last decade has seen renewed interest after the discovery of the sphingomyelin signal transduction pathway [3][4][5][6]. Ceramide appears to be a lipid second messenger in programmed cell death (apoptosis), cell differentiation and cell proliferation [reviews in 7-12; for the opposite point of view see 13], and sphingomyelinase is probably a major source of ceramide in the cells, although this is also a debated point. This contribution is based on a recent review [14] that we have modified according to several suggestions and criticisms received, and to which we have added what we consider as the most significant novel data to have appeared since.Two main aspects of sphingomyelinases are covered here, one corresponds to "classical enzymology", with a description of the known sphingomyelinases, and of their properties. The second is more directly related to our experimental work, and describes the interaction of sphingomyelinases with phospholipid bilayers, and the mutual influence of enzyme and substrate properties. One important function of sphingomyelinases may be related to changing membrane properties (charge, fluidity, permeability) by transforming sphingomyelin into ceramide. The present work does not cover the cell physiological effects of sphingomyelinases and/or ceramides, which are described in detail in the above-mentioned reviews.

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“…To date, a number of naturally occurring inhibitors of SMase have been described [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] . Several synthetic inhibitors, such as a carbamate analog, carbon-analog or fluorinated carbon-analog, that mimic the phosphate ester moiety of phosphocholine by substituting it with stable functional groups have also been developed [29][30][31][32][33][34] .…”

Section: Introductionmentioning

confidence: 99%

“…The syntheses of TOM-2-7 (10), TOM-2-18 (11) and TOM-2-37 (12) began with a glycerol derivative 42 prepared from D-Mannitol in four steps 43 . The [2,2 0 -bipyridin]-6-ylmethyl ether moiety was constructed by Williamson ether synthesis using NaH and 18, and the hydrolysis of the resulting ketal 43 gave a 98% yield of diol 44.…”

mentioning

confidence: 99%

Novel inhibitor of bacterial sphingomyelinase, SMY-540, developed based on three-dimensional structure analysis

Oda¹,

Imagawa

Kato³

et al. 2013

Journal of Enzyme Inhibition and Medicinal Chemistry

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Alutenusin, a Specific Neutral Sphingomyelinase Inhibitor, Produced by Penicillium sp. FO-7436.

Cited by 64 publications

References 7 publications

Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites

Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites

Sphingomyelinases and Their Interaction with Membrane Lipids

Novel inhibitor of bacterial sphingomyelinase, SMY-540, developed based on three-dimensional structure analysis

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