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Antagonistic effects of indoloquinazoline alkaloids on antimycobacterial activity of evocarpine
Author(s) -
Hochfellner C.,
Evangelopoulos D.,
Zloh M.,
Wube A.,
Guzman J.D.,
McHugh T.D.,
Kunert O.,
Bhakta S.,
Bucar F.
Publication year - 2015
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/jam.12753
Subject(s) - antimycobacterial , library science , biological sciences , medicine , biology , computer science , microbiology and biotechnology , tuberculosis , pathology , mycobacterium tuberculosis
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.