(1R,6S)-3-HYDROXY-4-METHYL-7-OXABICYCLO[4.1.0]HEPT-3-ENE-2,5-DIONE

Uses

Terreic Acid is an inhibitor of the catalytic activity of BTK. It is used in the method for treating SWI/SNF complex-deficient cancers comprising glutathione (GSH) metabolic pathway inhibitor.

Definition

ChEBI: Terreic acid is a 2-hydroxy-1,4-benzoquinone that is 5,6-epoxy. It is a natural product of Aspergillus terreus. It has an antibacterial activity explained by its inhibitory effect on bacterial enzymes MurA and GlmU. It is an inhibitor of Bruton's tyrosine kinase, and has an anti-tumoral activity against HeLa and EAC cells. It has a role as a mycotoxin, an antibacterial agent, an EC 2.5.1.7 (UDP-N-acetylglucosamine 1-carboxyvinyltransferase) inhibitor, an EC 2.3.1.* (acyltransferase transferring other than amino-acyl group) inhibitor, an EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, an Aspergillus metabolite and an antineoplastic agent. It is an arene epoxide, a tertiary alpha-hydroxy ketone, a member of monohydroxy-1,4-benzoquinones and a diketone. It is functionally related to a 2-hydroxy-1,4-benzoquinone.

Hazard

Mycotoxin; poison; mutagen.

Biological Activity

Selective inhibitor of Bruton's tyrosine kinase (BTK). Inhibits the interaction between PKCbII and BTK (IC 50 ~ 30 mM) and the catalytic activity of BTK but does not affect the activity of PKC. Has little effect on the activities of Lyn, Syk, PKA, casein kinase I, ERK1, ERK2 and p38 kinases.

Biochem/physiol Actions

Terreic acid (TA) is a covalent inhibitor of the bacterial cell wall biosynthetic enzyme MurA. The survival of most bacteria depends on the functionality of this cytosolic enzyme. The inactivation of MurA requires the presence of UDP-N-acetylglucosamine 1-Carboxyvinyl transferase, which catalyzes the first step in the biosynthesis of the bacterial cell wall. TA is more potent than the known MurA inhibitor Fosphomycin. TA was also found to severely inhibit the transcription of TNFα and IL-2. TA inhibits protein synthesis by blocking the formation of leucyl-tRNA in sensitive bacteria and inhibits the catalytic effect of Bruton′s tyrosine kinase (Btk), an important factor in B-cell and mast cell activation, by inducing conformational changes that prevent Protein Kinase C (PKC) from interacting with the Btk domain. Moreover, recent studies have demonstrated that TA exhibits a very high level of radical scavenging activity.

Purification Methods

Crystallise terreic acid from *C6H6, *C6H6/pet ether or hexane. Sublime it 80-100o/1mm. [Beilstein 17 IV 6698.]