title: Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa.
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.
authors.affiliation: Phytochemistry Laboratory, Research Center for the Natural Sciences, University of Santo Tomas, Espana St., 1015 Manila, Philippines. allan-patrick.macabeo@chemie.uni-regensburg.de
authors.forename: Allan Patrick G
authors.initials: AP
authors.lastname: Macabeo
authors.forename: Warren S
authors.initials: WS
authors.lastname: Vidar
authors.forename: Xinyu
authors.initials: X
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Decker
authors.forename: Jörg
authors.initials: J
authors.lastname: Heilmann
authors.forename: Baojie
authors.initials: B
authors.lastname: Wan
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Elano V
authors.initials: EV
authors.lastname: Galvez
authors.forename: Ma Alicia M
authors.initials: MA
authors.lastname: Aguinaldo
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Cordell
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004593:Electrophorus; D006736:Horses; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D010078:Oxazines; D053978:Pentacyclic Triterpenes / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D036902:Voacanga / Q000737:chemistry*; D014966:Xanthenes; D000094042:Lupanes
chemical_list: D000110:Acetylcholinesterase; D000470:Alkaloids; D000995:Antitubercular Agents; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; D026121:Indole Alkaloids; D010078:Oxazines; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D013141:Spiro Compounds; D014966:Xanthenes; C000598118:deoxyvobtusine; C000598117:globospiramine; C005843:resazurin; C010480:lupeol; D000094042:Lupanes