Gliotoxin-13C13 (Synonyms: Aspergillin-13C13)

Gliotoxin-¹³C₁₃ is intended for use as an internal standard for the quantification of gliotoxin by GC- or LC-MS. Gliotoxin is an immunosuppressive mycotoxin produced by pathogenic strains of Aspergillus and other fungi with diverse biological activities.^{1,2,3,4,5,6,7,8} It inhibits 20S proteasomal chymotrypsin activity (IC₅₀ = 10 μM), blocking the degradation of IκBα and preventing the activation of NF-κB.^2,3 Gliotoxin induces apoptosis in monocytes and dendritic cells and reduces phagocytosis by neutrophils.^4,5 It suppresses viral infection by Nipah and Hendra virus in HEK293T cells (IC₅₀s = 149 and 579 nM, respectively).⁶ Under reducing conditions, gliotoxin inhibits leukotriene A₄ hydrolase epoxide hydrolase activity, but not aminopeptidase activity, and leukotriene B₄ synthesis in neutrophils and monocytes.⁷ In vivo, gliotoxin (5 mg/kg) reduces LTB₄ plasma levels and blocks peritoneal neutrophil infiltration in a mouse model of peritonitis induced by zymosan A . It also inhibits geranylgeranyltransferase I and farnesyltransferase (IC₅₀s = 17 and 80 μM, respectively).⁸

1.Kwon-Chung, K.J., and Sugui, J.A.What do we know about the role of gliotoxin in the pathobiology of Aspergillus fumigatus•Med. Mycol.47(Suppl 1)S97-S103(2009) 2.Kroll, M., Arenzana-Seisdedos, F., Bachelerie, F., et al.The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasomeChem. Biol.6(10)689-698(1999) 3.Pahl, H.L., Krauss, B., Schulze-Osthoff, K., et al.The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-κBJ. Exp. Med.183(4)1829-1840(1996) 4.Anselmi, K., Stolz, D.B., Nalesnik, M., et al.Gliotoxin causes apoptosis and necrosis of rat Kupffer cells in vitro and in vivo in the absence of oxidative stress: Exacerbation by caspase and serine protease inhibitionJ. Hepatol.47(1)103-113(2007) 5.Orciuolo, E., Stanzani, M., Canestraro, M., et al.Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: Implications for the pathogenesis of invasive aspergillosisJ. Leukoc. Biol.82(4)839-848(2007) 6.Aljofan, M., Sganga, M.L., Lo, M.K., et al.Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitroVirol. J.6187(2009) 7.KÖnig, Pace, S., Pein, H., et al.Gliotoxin from Aspergillus fumigatus abrogates leukotriene B4 formation through inhibition of leukotriene A4 hydrolaseCell. Chem. Biol.26(4)524-534(2019) 8.Vigushin, D.M., Mirsaidi, N., Brooke, G., et al.Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivoMed. Oncol.21(1)21-30(2004)