Description
Bis(methylthio)gliotoxin is a fungal metabolite originally isolated from
G. deliquescens that has diverse biological activities. It inhibits PAF- and collagen-induced platelet aggregation in rabbit platelet-rich plasma (IC
50s = 8.4 and 84.2 μM, respectively) but has no effect on arachidonic acid- or ADP-induced platelet aggregation (IC
50s = >400 μM).
Bis(methylthio)gliotoxin inhibits growth of HCT116 colon cancer cells (IC
50 = 23.56 μM). It inhibits PAF-induced bronchoconstriction in guinea pigs when administered at a dose of 0.1 mg/kg and is less toxic to mice (LD
50 = >500 mg/kg) than gliotoxin .
Bis(methylthio)gliotoxin has been used as a serum biomarker in patients infected with invasive aspergillosis.
Uses
Bis(methylthio)gliotoxin (FR-49175) is an antiphagocytic metabolite.
Enzyme inhibitor
This naturally occurring indole derivative (FW = 356.47 g/mol; CAS 74149- 38-5), also known as bis(methylthio)gliotoxin and dimethylgliotoxin, is a platelet-acivating factor (PAF) antagonist that inhibits PAF-induced platelet aggregation. The parent compound, gliotoxin is a dual inhibitor of famesyltransferase and geranylgeranyl-transferase. Bisdethiobis(methylthio)gliotoxin is a minor metabolite of Gliocladium deliquescens, Radiocarbon tracer experiments showed it is formed, apparently irreversibly, from gliotoxin. It has also been synthesized from gliotoxin by reduction and methylation. Bisdethio-bis(methylthio)gliotoxin also binds Cu+ and Ag+ ions.
References
[1] G. W. KIRBY. Biosynthesis of bisdethiobis(methylthio)gliotoxin, a new metabolite of Gliocladium deliquescens[J]. Journal of The Chemical Society-perkin Transactions 1, 1980, 31 1: 119-121. DOI:
10.1039/p19800000119[2] M OKAMOTO. Studies of platelet activating factor (PAF) antagonists from microbial products. I. Bisdethiobis(methylthio)gliotoxin and its derivatives.[J]. Chemical & pharmaceutical bulletin, 1986, 34 1: 340-344. DOI:
10.1248/cpb.34.340[3] BáRBARA S. F. RODRIGUES. Bioprospection of Cytotoxic Compounds in Fungal Strains Recovered from Sediments of the Brazilian Coast[J]. Chemistry & Biodiversity, 2015, 12 3: 432-442. DOI:
10.1002/cbdv.201400193[4] M OKAMOTO. Studies of platelet activating factor (PAF) antagonists from microbial products. II. Pharmacological studies of FR-49175 in animal models.[J]. Chemical & pharmaceutical bulletin, 1986, 34 1: 345-348. DOI:
10.1248/cpb.34.345[5] MARIA P. DOMINGO . Bis(methyl)gliotoxin proves to be a more stable and reliable marker for invasive aspergillosis than gliotoxin and suitable for use in diagnosis[J]. Diagnostic microbiology and infectious disease, 2012, 73 1: Pages 57-64. DOI:
10.1016/j.diagmicrobio.2012.01.012
