Abstract
A new sorbicillinoid polyketide, dihydrotrichodimerol (2), along with known trichodimerol (1), and rezishanones C (3) and D (4) were isolated by bioassay-guided fractionation from an unidentified fungal strain. Dihydrotrichodimerol (2) specifically activated peroxisome proliferator-activated receptor γ with an ED50 value of 80 ng/ml as measured by a transactivation assay using a chimeric hPPAR/GAL4 system without affecting peroxisome proliferator-activated receptors α and δ. On the other hand, compounds 1 and 2 suppressed the production of tumor necrosis factor-α and nitric oxide in LPS-stimulated RAW264.7 cells to a similar extent.
Similar content being viewed by others
Article PDF
References
Issemann I, Green S . Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347: 645–650 ( 1990)
Daynes RA, Jones DC . Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2: 748–759 ( 2002)
Murphy GJ, Holder JC . PPAR-γ agonists: therapeutic role in diabetes, inflammation and cancer. Trends Pharmacol Sci 21: 469–474 ( 2000)
Hwang BY, Lee JH, Nam JB, Kim HS, Hong YS, Lee JJ . Two new furanoditerpenes from Saururus chinenesis and their effects on the activation of peroxisome proliferator-activated receptor γ. J Nat Prod 65: 616–617 ( 2002)
Andrade R, Ayer WA, Mebe PP . The metabolites of Trichoderma longibrachiatum. Part 1. Isolation of the metabolites and the structure of trichodimerol. Can J Chem 70: 2526–2535 ( 1992)
Gao Q, Leet JE, Thomas ST, Matson JA, Bancroft DP . Crystal structure of trichodimerol. J Nat Prod 58: 1817–1821 ( 1995)
Maskey RP, Grun-Wollny I, Laatsch H . Sorbicillin analogues and related dimeric compounds from Penicillium notatum. J Nat Prod 68: 865–870 ( 2005)
Abe N, Murata T, Hirota A . Novel DPPH radical scavengers, bisorbicillinol and demethyltrichodimerol, from a fungus. Biosci Biotechnol Biochem 62: 661–666 ( 1998)
Mazzucco CE, Warr G . Trichodimerol (BMS-182123) inhibits lipopolysaccharide-induced eicosanoid secretion in THP-1 human monocytic cells. J Leukocyte Biol 60: 271–277 ( 1996)
Sperry S, Samuels GJ, Crews P . Vertinoid polyketides from the saltwater culture of the fungus Trichoderma longibrachiatum separated from a Haliclona marine sponge. J Org Chem 63: 10011–10014 ( 1998)
Warr GA, Veitch JA, Walsh AW, Hesler GA, Pirnik DM, Leet JE, Lin PF, Medina IA, McBrien KD, Forenza S, Clark JM, Lam KS . BMS-182123, a fungal metabolite that inhibits the production of TNF-α by macrophages and monocytes. J Antibiot 49: 234–240 ( 1996)
Abe N, Arakawa T, Yamamoto K, Hirota A . Biosynthesis of bisorbicillinoid in Trichoderma sp. USF-2690; evidence for the biosynthetic pathway, via sorbicillinol, of sorbicillin, bisorbicillinol, bisorbibutenolide, and bisorbicillinolide. Biosci Biotechnol Biochem 66: 2090–2099 ( 2002)
Abe N, Sugimoto O, Arakawa T, Tanji K, Hirota A . Sorbicillinol, a key intermediate of bisorbicillinoid biosynthesis in Trichoderma sp. USF-2690. Biosci Biotechnol Biochem 65: 2271–2279 ( 2001)
Abe N, Yamamoto K, Arakawa T, Hirota A . The biosynthesis of bisorbicillinoids: evidence for a biosynthetic route from bisorbicillinol to bisorbibutenolide and bisorbicillinolide. Chem Commun: 23–24 ( 2001)
Barnes-Seeman D, Corey EJ . A two-step total synthesis of the natural pentacycle trichodimerol, a novel inhibitor of TNF-α production. Org Lett 1: 1503–1504 ( 1999)
Nicolaou KC, Vassilikogiannakis G, Simonsen KB, Baran PS, Zhong YL, Vidali VP, Pitsinos EN, Couladouros EA . Biomimetic total synthesis of bisorbicillinol, bisorbibutenolide, trichodimerol, and designed analogues of the bisorbicillinoids. J Am Chem Soc 122: 3071–3079 ( 2000)
Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM . 15-Deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 83: 803–812 ( 1995)
Lee JH, Koo TH, Hwang BY, Lee JJ . Kaurane diterpene, kamebakaurin, inhibits NF-κB by directly targeting the DNA-binding activity of p50 and blocks the expression of antiapoptotic NF-κB target genes. J Biol Chem 277: 18411–18420 ( 2002)
Abe N, Murata T, Hirota A . Novel oxidized sorbicillin dimers with 1,1-diphenyl-2-picryl-radical scavenging activity from a fungus. Biosci Biotechnol Biochem 62: 2120–2126 ( 1998)
Shirota O, Pathak V, Hossain CF, Sekita S, Takatori K, Satake M . Structural elucidation of trichotetronines: polyketides possessing a bicyclo[2.2.2]octane skeleton with a tetronic acid moiety isolated from Trichoderma sp. J Chem Soc Perkin Trans I 1997: 2961–2964 ( 1997)
Trifonov LS, Hilpert H, Floersheim P, Dreiding AS, Rast DM, Skrivanova R, Hoesch L . Bisvertinols: a new group of dimeric vertinoids from Verticillium intertextum. Tetrahedron 42: 3157–3179 ( 1986)
Castrillo A, Mojena M, Hortelano S, Bosca L . Peroxisome proliferator-activated receptor-γ-independent inhibition of macrophage activation by the non-thiazolidinedione agonist L-796449: Comparison with the effects of 15-deoxy-Δ12,14-prostaglandin J2 . J Biol Chem 276: 34082–34088 ( 2001)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, D., Lee, J., Cai, X. et al. Fungal Metabolites, Sorbicillinoid Polyketides and Their Effects on the Activation of Peroxisome Proliferator-activated Receptor γ. J Antibiot 58, 615–620 (2005). https://doi.org/10.1038/ja.2005.84
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ja.2005.84
Keywords
This article is cited by
-
The role of PKAc1 in gene regulation and trichodimerol production in Trichoderma reesei
Fungal Biology and Biotechnology (2019)
-
Bisorbicillinoids Produced by the Fungus Trichoderma citrinoviride Affect Feeding Preference of the Aphid Schizaphis graminum
Journal of Chemical Ecology (2009)
-
The fungal secondary metabolite trichodimerol inhibits TGF-β dependent cellular effects and tube formation of MDA-MB-231 cells
Investigational New Drugs (2009)