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        Antagonistic effects of indoloquinazoline alkaloids on antimycobacterial activity of evocarpine

        Author
        Hochfellner, C.
        Evangelopoulos, D.
        Zloh, Mire
        Wube, A.
        Guzman, J. D.
        Mchugh, T. D.
        Kunert, O.
        Bhakta, S.
        Bucar, F.
        Attention
        2299/16967
        Abstract
        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<sup>-1</sup>) 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. Copyright
        Publication date
        2015-04-01
        Published in
        Journal of Applied Microbiology
        Published version
        https://doi.org/10.1111/jam.12753
        Other links
        http://hdl.handle.net/2299/16967
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