Zaragozic acid A Chemical Properties

alpha 

D22 +18.3° (c = 0.60 in CHCl3); D25 +37° (c = 1.29 in methanol)

Boiling point:

850.1±65.0 °C(Predicted)

Density 

1.35±0.1 g/cm3(Predicted)

storage temp. 

−20°C

solubility 

Soluble in DMSO

form 

solid

pka

1.47±0.70(Predicted)

color 

white to light tan

CAS DataBase Reference

142561-96-4

Safety Information

WGK Germany 

3

Zaragozic acid A Usage And Synthesis

Chemical Properties

White to light tan solid. Soluble in ethanol (10 mg/ml), methanol, DMF, DMSO (10 mg/ml), and water (moderate).

Uses

Zaragozic acid A is the major metabolite of a class of unusual bicyclic tricarboxylic acids, produced by a number of fungi in the genera Curvularia, Exserohilum, Setosphaeria and others, discovered at Merck and Glaxo in the early 1990s. In nature, zaragozic acid A acts as broad spectrum antifungal but its mode of action as an inhibitor of squalene synthase, involved in sterol biosynthesis, lead to investigation as a cholesterol lowering agent. Zaragozic acid A prepared by BioAustralis is presented as the free acid rather than the tri-sodium salt to avoid stability problems associated with hydrolysis of the salt.

Definition

ChEBI: Zaragozic acid A is a polyketide isolated from fungi that is a potent inhibitor of fungal and mammalian squalene synthase. It has a role as an EC 2.5.1.21 (squalene synthase) inhibitor and a fungal metabolite. It is a tricarboxylic acid, an acetate ester, a cyclic ketal, an oxabicycloalkane, a tertiary alcohol and a polyketide.

Application

Zaragozic Acid A is a squalene synthetase inhibitor. it targeted squalene synthase and lowered the cholesterol levels in vivo of marmosets.

Biological Activity

Zaragozic acid A is an inhibitor of acute liver cholsterol synthesis (50% inhibition dose 200 μg/ kg) with Ki value of 78pM. It inhibited cholesterol synthesis in Hep G2 cells.

in vitro

zaragozic acid a, as well as it two analogs zaragozic acid b and c were discovered from an unidentified sterile fungal culture, spororniella intermedia, and leptodontium elatius, respectively. zaragozic acid a, b and c were reported to be three potent competitive inhibitors of rat liver squalene synthase with ki values of 78 pm, 29 pm, and 45 pm, respectively. in addition, zaragozic acid a, b and c could also inhibite cholesterol synthesis in hep g2 cells [1].

in vivo

in the mouse model, zaragozic acid a was found to be an inhibitor of acute hepatic cholesterol synthesis (50% inhibitory dose of 200 μg/kg). the in-vivo inhibition of squalene synthase was accompanied by an accumulation of label from [3hjmevalonate into farnesyl diphosphate, farnesol, as well as organic acids. in summary, these data showed the zaragozic acids were a new class of therapeutic agents with potential for the hypercholesterolemia treatment [1].

References

[1] bergstrom jd,kurtz mm,rew dj,amend am,karkas jd,bostedor rg,bansal vs,dufresne c,vanmiddlesworth fl,hensens od, et al. zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. proc natl acad sci u s a.1993 jan 1;90(1):80-4.

Zaragozic acid A(142561-96-4)Related Product Information

• SQUALESTATIN
• 2-METHYLCITRIC ACID
• 2-DECYLSUCCINIC ACID
• OCTYLSUCCINIC ACID
• 2-HYDROXY-2-ISOPROPYLSUCCINIC ACID
• 2-BUTYL-4,4,6-TRIMETHYL-1,3-DIOXANE
• Zaragozic acid A
• 2-METHYL-TETRAHYDRO-FURAN-2-CARBOXYLIC ACID
• DL-LEUCIC ACID
• Hydroxycitric acid
• 5,5-DIETHOXYPENTAN-1-OL