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.

A 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 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).