European Journal of Medicinal Chemistry 2011-07-01

Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa.

Allan Patrick G Macabeo, Warren S Vidar, Xinyu Chen, Michael Decker, Jörg Heilmann, Baojie Wan, Scott G Franzblau, Elano V Galvez, Ma Alicia M Aguinaldo, Geoffrey A Cordell

Index: Eur. J. Med. Chem. 46 , 3118-23, (2011)

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Abstract

Globospiramine (1), a new spirobisindole alkaloid possessing an Aspidosperma-Aspidosperma skeleton, together with deoxyvobtusine (2), deoxyvobtusine lactone (3), vobtusine lactone (4) and lupeol (5), were isolated and identified from Voacanga globosa through a bioassay-guided purification. The gross structure and absolute stereochemistry of 1 were established by circular dichroism spectroscopy, HR-MS and unambiguous NMR spectroscopic experiments. In addition, a new biogenetic pathway for the formation of the spiro-Aspidosperma-Aspidosperma skeleton is proposed. Alkaloid 1 showed potent antituberculosis activity against Mycobacterium tuberculosis H(37)Rv as evidenced in microplate Alamar blue assay (MIC = 4 μg/mL) and low-oxygen recovery assay (LORA (MIC = 5.2 μg/mL). The bisindole alkaloids also exhibited promising activity against acetylcholinesterase and, especially butyrylcholinesterase, with deoxyvobtusine (2) (IC(50) = 6.2 μM) as the most strongly inhibiting compound. This study extends the variety of alkaloid structural platforms which exhibit antimycobacterial and anticholinesterase activity.Copyright © 2011 Elsevier Masson SAS. All rights reserved.