Roquefortine

389.45000

389.45

2933990090

90.12000

2.78780

1.37g/cm3

202-205 °C

768.3ºC

418.4ºC

1.686

-20ºC

UN 2811 6.1/PG 2

R23/24/25

S22; S36/37/39; S45

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Roquefortine is a metabolite of P. roqueforte (a fungi used as a source of proteolytic and lipolytic enzymes during maturation of blue-veined cheeses).

Residues of roquefortine could be analysed in rumen fluid, feces, liver, bile, kidneys, and muscle /eighteen female sheep received amounts of roquefortine equivalent to concentrations of zero, 5 and 25 mg/kg silage over a period of 16 to 18 days/.

Roquefortine interaction with rat and human liver cytochromes P450 was monitored by difference UV-vis spectroscopy. It was found to interact with different forms of the cytochromes, giving rise to a type II difference spectrum, characteristic of the binding of an amino function to the heme iron. Roquefortine exhibited high affinity for microsomes from rats treated with various inducers, the K(s) values being in the range 0.2-8 microM. Similar results were observed with human P450 enzymes 1A1, 1A2, 2D6, and 3A4. Roquefortine had no effect on NAPDH cytochrome c reductase. Therefore, inhibition of NADPH consumption was observed using various rat liver microsomes alone or in the presence of 100 microM testosterone in the case of dexamethasone (DEX)-rat microsomes. Enzymatic inhibition was studied in terms of P450 3A activities, i.e., testosterone 6beta-hydroxylase (IC(50) around 10 microM) or bromocriptine metabolism (IC(50) > 50 microM) using DEX-rat liver microsomes or P450 3A4, benzphetamine N-demethylase using phenobarbital-rat liver microsomes (IC(50) > 30 microM), and ethoxyresorufin metabolism using 3-methylcholanthrene-rat liver microsomes (IC(50) 0.1 microM), P450 1A1, and 1A2. Roquefortine was compared with compounds of similar structure: cyclo(Phe-His), cyclo(Phe-dehydroHis), cyclo(Trp-His), phenylahistin. These studies indicate that the =N- imidazole moiety coordinates with the heme iron, and suggest that the dehydroHis moiety and the presence of a fused tetracycle play an important part in roquefortine inhibitory power.

isoroquefortine C