Antagonistic effects of indoloquinazoline alkaloids on antimycobacterial activity of evocarpine.
- Resource Type
- Article
- Authors
- Hochfellner, C.; Evangelopoulos, D.; Zloh, M.; Wube, A.; Guzman, J.D.; McHugh, T.D.; Kunert, O.; Bhakta, S.; Bucar, F.
- Source
- Journal of Applied Microbiology. Apr2015, Vol. 118 Issue 4, p864-872. 9p. 1 Color Photograph, 1 Diagram, 4 Charts, 1 Graph.
- Subject
- *QUINAZOLINE
*ANTIBACTERIAL agents
*MYCOBACTERIAL disease treatment
*HERBAL medicine
*THERAPEUTICS
THERAPEUTIC use of alkaloids
THERAPEUTIC use of plant extracts
- Language
- ISSN
- 1364-5072
Aims The interaction of quinolone and indoloquinazoline alkaloids concerning their antimycobacterial activity was studied. Methods and 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. Significance and Impact of the Study 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. [ABSTRACT FROM AUTHOR]