title: Antagonistic effects of indoloquinazoline alkaloids on antimycobacterial activity of evocarpine.
abstract: OBJECTIVE
  The interaction of quinolone and indoloquinazoline alkaloids concerning their antimycobacterial activity was studied.
  
  
  RESULTS
  The antimycobacterial and modulating activity of evodiamine (1), rutaecarpine (2) and evocarpine (3) was tested on mycobacteria including three multidrug-resistant (MDR) clinical isolates of Mycobacterium tuberculosis. Antagonistic effects were concluded from fractional inhibitory concentration (FICI) values. Interaction energies of the compounds were calculated using GLUE docking module implemented in GRID. 1 and 2 exhibited weak inhibition of rapidly growing mycobacteria, however, 1 was active against Myco. tuberculosis H37Rv (MIC = 10 mg l(-1) ) while 2 was inactive. Both 1 and 2 showed a marked antagonistic effect on the susceptibility of different mycobacterial strains to 3 giving FICI values between 5 and 9. The interaction energies between compounds 1 and 2 with compound 3 suggested the possibility of complex formation in solution.
  
  
  CONCLUSIONS
  Indoloquinazoline alkaloids markedly reduce the antimycobacterial effect of the quinolone alkaloid evocarpine. Complex formation may play a role in the attenuation of its antimycobacterial activity.
  
  
  CONCLUSIONS
  This study gives a striking example of antagonism between compounds present in the same plant extract which should be considered in natural product based screening projects.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Graz, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Hochfellner
authors.forename: D
authors.initials: D
authors.lastname: Evangelopoulos
authors.forename: M
authors.initials: M
authors.lastname: Zloh
authors.forename: A
authors.initials: A
authors.lastname: Wube
authors.forename: J D
authors.initials: JD
authors.lastname: Guzman
authors.forename: T D
authors.initials: TD
authors.lastname: McHugh
authors.forename: O
authors.initials: O
authors.lastname: Kunert
authors.forename: S
authors.initials: S
authors.lastname: Bhakta
authors.forename: F
authors.initials: F
authors.lastname: Bucar
mesh_terms: D000470:Alkaloids / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004336:Drug Antagonism; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000037:antagonists & inhibitors*; D015363:Quinolones / Q000037:antagonists & inhibitors*; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D010936:Plant Extracts; D011799:Quinazolines; D015363:Quinolones; C059242:evocarpine
keywords: Euodia; antagonism; evocarpine; evodiamine; modelling; mycobacteria; rutaecarpine