| In vitro: |
| J Appl Microbiol. 2015 Apr;118(4):864-72. | | Antagonistic effects of indoloquinazoline alkaloids on antimycobacterial activity of evocarpine.[Pubmed: 25604161] | 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. | | Planta Medica, 2012, 78(11):1142-1142. | | Characterization of in vitro metabolites of evocarpine in rat liver microsomes and their influence on antibacterial activity[Reference: WebLink] |
METHODS AND RESULTS:
After incubation of Evocarpine, the major bioactive compound of the n-hexane extract of the fruits of Evodiae fructus, with rat liver microsomes (S9 mix) nine metabolites were identified by their characteristic product ions using LC-PDA-ESI-MS analysis. The main biotransformation reactions observed were hydroxylation, hydration, dehydrogenation and N-demethylation. Comparison of incubation times between 1 and 72 hours showed no qualitative difference in biotransformation.
CONCLUSIONS:
In order to assess the influence of metabolism on the antibacterial activity of Evocarpine and the crude extract, the test solutions were pre-incubated with the S9 mix prior the determination of the minimum inhibitory concentration (MIC), which revealed a four-fold increase of the MIC against Mycobacterium smegmatis ATCC 14468 for pre-incubation times of 1, 24 and 72 hours for the crude extract and a sixteen-fold increase for Evocarpine for a pre-incubation time of 1 hour. |
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