Diarylquinoline antibiotic

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Diarylquinoline antibiotics (also just Diarylquinoline , DARQ) are a group of antibiotic substances that work against mycobacteria .

First therapeutically used Diarylchinolin is Bedaquiline

Its mechanism of action starts with the c subunit of mycobacterial ATP synthase , an enzyme that is important for cellular energy metabolism. The effect is bactericidal . The effect on ATP synthase is very specific; the eukaryotic enzyme is not inhibited. DARQ are therapeutically important for the treatment of tuberculosis , which is resistant to other agents (MDR-TB, multi drug resistant Mycobacterium tuberculosis ).

Quinoline structural element of the diarylquinoline antibiotics

In addition to the mechanism of action, the DARQ also differ structurally from other antimicrobial quinoline (including mefloquine ) and quinolone active ingredient groups (e.g. fluoroquinolones ). A key difference is the specificity of the functionalized side chains that DARQ carry in position 3 of the quinoline skeleton .

The first drug approved for the treatment of MDR tuberculosis is bedaquiline . Experimental DARQ are TBAJ-587 and TBAJ-876 , which have shown better efficacy than bedaquiline in animal models with a more favorable side effect profile.

Individual evidence

  1. ↑ Koul A, Dendouga N, Vergauwen K, Molenberghs B, Vranckx L: Diarylquinolines Target Subunit C of Mycobacterial ATP Synthase. June 2007, accessed May 7, 2020 .
  2. ↑ Haagsma Ac, Abdillahi-Ibrahim R, Wagner Mj, Krab K, Vergauwen K: Selectivity of TMC207 Towards Mycobacterial ATP Synthase Compared With That Towards the Eukaryotic Homologue. March 2009, accessed May 7, 2020 .
  3. ↑ K. Andries et al .: A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis . In: Science . tape 307 (2005) , pp. 223-227 , doi : 10.1126 / science.1106753 .
  4. ↑ Kiwi researchers in breakthrough treatment for deadly drug-resistant tuberculosis , Biotech New Zealand, November 1, 2019.
  5. ↑ HS Sutherland et al .: 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. In: Bioorganic & Medicinal Chemistry . tape 27 (2019) , pp. 1292-1307 , doi : 10.1016 / j.bmc.2019.02.026 .
  6. ↑ M. Krutikov et al .: New and repurposed drugs . In: Tuberculosis. European Respiratory Society (ERS). Ed .: GB Miglioris et al. 2018. Limited preview in Google Book Search.