Bedaquinoline has the same bactericidal activity against both sensitive and resistant strains of mycobacterium tuberculosis as well as on dormant bacteria.
Fig: Synthetic route of Bedaquiline
Labeled Bedaquiline, intended for use as an internal standard for the quantification of Bedaquiline by GC- or LC-mass spectrometry.
Bedaquinoline is easy for oral assimilation. The bioavailability of Bedaquinoline taken with food is twice higher than when taken with an empty stomach. It reaches its blood concentration in 5 hours after taken and has a plasma protein binding rate of 99.9% as well as a plasma half-life of 173 hours. Bedaquinoline can be widely distributed in human body with a homeostasis distribution volume of 1000Ｌ. Its clearance rate is low enough and the elimination half-life is 5.5 months. Bedaquinoline is metabolize into metabolite 1~8 in the demethylation mainly through CYP3A4 and partly though CYP2C8 and CYP2C19. Metabolite 2 （M2）, the most important metabolite, which has only 1/3-1/6 the activity of Bedaquinoline, yet present a more strong cytotoxicity and is more likely to cause the drug-induced phospholipidosis. Bedaquinoline and its metabolites are mostly excreted by feces, only 1% to 4% by urine.
The proton pump on the cell’s ATP synthetase, which is a crucial enzyme for M. tuberculosis (TB) to synthesize ATP, is the unique and specific locus of Bedaquinoline.
After the combination onto the oligomer and lipoprotein subunit c, Bedaquinoline can inhibit the synthesis of ATP and bring the death to the bacterium cell. Compared with those existing anti-TB medicines, it presents a novel pharmacology and no cross resistance effect was found between Bedaquinoline and other anti-TB medicines. The gene sequence of the subunit c of ATP synthetase is named as atpE, whose amino acid sequence is highly conservative. The resistance of TB to Bedaquinoline comes from its reduced combination onto subunit c of ATP synthetase due to the mutation of the 63rd or 66th on atpE.
Bedaquiline, formally called (1R, 2S)-1-(6-Bromo-2-methoxy-3-quinolinyl)-4-(dimethylamino)-2-(1-naphthyl)-1-phenyl-2-butanol in chemistry and known as Sirturo in commercial, is a new anti-mycobacterial medicine of diarylquinolines. It impinges on the
ATP synthesis of Mycobacterium tuberculosis by inhibiting the activity of proton pump on the cell’s ATP synthetase, and thereby eliminates M. tuberculosis (TB). It’s used for adult multi-drug resistant tuberculosis (MDR-PTB).
Common adverse reactions are nausea, headache, arthralgia, loss of appetite, vomiting and rash, dizziness, elevated transaminase, increased hemodiastase, muscle pain, diarrhea and prolonged TQ interval.
1.The allergic to this product;
2.Patients suffer serious dysfunction of heart, liver, kidney (relative contraindication);
3.Pregnant women, lactating women, children, the old and co-infected HIV sufferers (relative contraindication).
(αS,βR)-Bedaquiline is a diarylquinoline derivative that acts as a mycobacterial inhibitor. Bedaquiline shows promise as potential drug in the treatment of tuberculosis.