74149-38-5

Basic information

• Product Name: BIS(METHYLTHIO)GLIOTOXIN
• Synonyms: BIS(METHYLTHIO)GLIOTOXIN;FR-49175;bis-dethio-bis(methylthio)gliotoxin;gliotoxin, bis-dethio-bis(methylthio)-;(3R)-2,3,5aβ,6,10,10a-Hexahydro-6β-hydroxy-3β-(hydroxymethyl)-2-methyl-3α,10aα-bis(methylthio)pyrazino[1,2-a]indole-1,4-dione;2,3,5aβ,6,10,10a-Hexahydro-6β-hydroxy-3β-(hydroxymethyl)-2-methyl-3,10aα-bis(methylthio)pyrazino[1,2-a]indole-1,4-dione;Bis(methylthio)gliotoxin (FR-49175)
• CAS NO: 74149-38-5
• Molecular Formula: C₁₅H₂₀N₂O₄S₂
• Molecular Weight: 356.46
• Mol File: 74149-38-5.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 669.6 °C at 760 mmHg
• Flash Point: 358.8 °C
• Appearance: Colorless oil
• Density: 1.49 g/cm³
• Vapor Pressure: 8.57E-21mmHg at 25°C
• Refractive Index: 1.701
• Storage Temp.: −20°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 12.69±0.60(Predicted)
• CAS DataBase Reference: BIS(METHYLTHIO)GLIOTOXIN(CAS DataBase Reference)
• NIST Chemistry Reference: BIS(METHYLTHIO)GLIOTOXIN(74149-38-5)
• EPA Substance Registry System: BIS(METHYLTHIO)GLIOTOXIN(74149-38-5)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36
• RIDADR: 1544
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 74149-38-5(Hazardous Substances Data)

Usage

Description

Bis(methylthio)gliotoxin, also known as FR-49175, is a fungal metabolite originally isolated from G. deliquescens. It exhibits a range of biological activities, including antiphagocytic properties, and has demonstrated potential in various medical applications due to its ability to inhibit specific biological processes.

Uses

Used in Pharmaceutical Industry:
Bis(methylthio)gliotoxin is used as an inhibitor for platelet aggregation, specifically in the prevention of PAFand collagen-induced aggregation in rabbit platelet-rich plasma. This application is significant for the treatment and management of conditions related to blood clotting and cardiovascular health.
Used in Cancer Research:
In the field of oncology, Bis(methylthio)gliotoxin is used as an inhibitor of HCT116 colon cancer cell growth, with an IC50 value of 23.56 μM. This suggests its potential utility in the development of targeted therapies for colorectal cancer.
Used in Respiratory Medicine:
Bis(methylthio)gliotoxin is used to inhibit PAF-induced bronchoconstriction in guinea pigs when administered at a dose of 0.1 mg/kg. This application highlights its potential in the treatment of respiratory conditions, such as asthma or other bronchoconstrictive disorders.
Used in Diagnostics:
As a serum biomarker, Bis(methylthio)gliotoxin is used for the detection of invasive aspergillosis in patients. This application aids in the early diagnosis and timely treatment of this invasive fungal infection, which is particularly important for immunocompromised individuals.
Used in Toxicology:
Bis(methylthio)gliotoxin has been evaluated for its toxicity in mice, with an LD50 value of >500 mg/kg. This information is crucial for assessing its safety profile and determining appropriate dosages for potential therapeutic use.

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.

InChI:InChI=1/C15H20N2O4S2/c1-16-12(20)14(22-2)7-9-5-4-6-10(19)11(9)17(14)13(21)15(16,8-18)23-3/h4-6,10-11,18-19H,7-8H2,1-3H3/t10-,11-,14+,15+/m0/s1

Upstream product

• 67-99-2 gliotoxin 
• 74-88-4 methyl iodide 

Relevant articles and documents

Opposed effects of enzymatic gliotoxin N - And S -methylations

Gliotoxin (1), a virulence factor of the human pathogenic fungus Aspergillus fumigatus, is the prototype of epipoly(thiodioxopiperazine) (ETP) toxins. Here we report the discovery and functional analysis of two methyl transferases (MTs) that play crucial roles for ETP toxicity. Genome comparisons, knockouts, and in vitro enzyme studies identified a new S-adenosyl-l- methionine-dependent S-MT (TmtA) that is, surprisingly, encoded outside the gli gene cluster. We found that TmtA irreversibly inactivates ETP by S-alkylation and that this detoxification strategy appears to be not only limited to ETP producers. Furthermore, we unveiled that GliN functions as a freestanding amide N-MT. GliN-mediated amide methylation confers stability to ETP, damping the spontaneous formation of tri- and tetrasulfides. In addition, enzymatic N-alkylation constitutes the last step in gliotoxin biosynthesis and is a prerequisite for the cytotoxicity of the molecule. Thus, these specialized alkylating enzymes have dramatic and fully opposed effects: complete activation or inactivation of the toxin.