Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa

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 H37Rv 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) (IC50 = 6.2 μM) as the most strongly inhibiting compound. This study extends the variety of alkaloid structural platforms which exhibit antimycobacterial and anticholinesterase activity.

Graphical abstractA new spirobisindole alkaloid globospiramine (1) and deoxyvobtusine (2) were identified from Voacanga globosa as new alkaloid congeners with potent antituberculosis and butyrylcholinesterase activity respectively.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A new bisindole alkaloid, globospiramine (1) was identified from Voacanga globosa. ► Globospiramine displays potent antituberculosis activity in vitro. ► Deoxyvobtusine (2) exhibits high activity against butyrylcholinesterase (BChE).