Definition
ChEBI: A 2,4'-bi-1,3-thiazole substituted at the 4-position with a (1E,3S,4R,5E)-7-amino-3,5-dimethoxy-4-methyl-7-oxohepta-1,5-dien-1-yl] group and at the 2'-position with a (2S
Biochem/physiol Actions
Myxothiazol, an antibiotic with activity against fungi and insects, is a strong inhibitor of mitochondrial cytochrome b/c1-segment of respiratory chain. Myxothiazol binds to the quinol oxidation (Qo) site of the bc1 complex, blocking electron transfer to the Rieske iron-sulfur protein in the mitochondrial respiratory chain. Oxygen consumption blockage leads to a cytostatic effect that could be reversed. Myxothiazol, as other Epothilones, which are known for their anti tumor activity, contains a thiazole ring that is formed by the incorporation of cysteine into the polyketide backbone.
in vivo
Myxothiazol (i.p.; 0.56 mg/kg; daily for 4 days)-induced complex III inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality[3].
| Animal Model: | C57Bl/J6 mice[3] |
| Dosage: | 0.56 mg/kg |
| Administration: | I.p.; 24 hours intervals for at most 4 times |
| Result: | A reversible complex III activity decrease to 50% of control value occurred at 2 h post-injection. At 74 h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found.
|
