Antimycobacterial Activities of the Zanthoxylum leprieurii Metabolite Adubangoamide and Non-Natural Fagaramide Analogues

Le résumé fourni par la source

trans -Fagaramide ( 1 ) and adubangoamide ( 2 ) are natural products with a cinnamic acid amide skeleton that have recently been isolated from Zanthoxylum leprieurii, a medicinal plant used locally in Uganda for the treatment of tuberculosis. Insufficient quantities of material from the natural source originally prevented the antimycobacterial evaluation of the new natural product 2 . Herein, a synthesis of 2 is reported, and its antimycobacterial activity was determined using the synthetic material. Adubangoamide ( 2 ) is three times more active against the drug-susceptible M. tuberculosis strain H 37 Rv than trans -fagaramide ( 1 ), with an MIC value of 10.0 μM. In addition, we synthesized eight non-natural analogues of trans -fagaramide ( 1, MIC = 32.0 μM against H 37 Rv strain), in which benzylamide groups mimic the isobutylamide part of the trans -fagaramide structure. Five out of eight synthetic analogues are more active than the parent natural product: 11b (MIC = 6.0 μM), 11d (21.0 μM), 11e (6.1 μM), 11g (17.0 μM), and 11h (4.5 μM).

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