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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa
Allan Patrick G Macabeo1, Warren S Vidar, Xinyu Chen
1Phytochemistry Laboratory, Research Center for the Natural Sciences, University of Santo Tomas, Espana St., 1015 Manila, Philippines. allan-patrick.macabeo@chemie.uni-regensburg.de
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.
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