Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa

Eur J Med Chem. 2011 Jul;46(7):3118-23. doi: 10.1016/j.ejmech.2011.04.025. Epub 2011 Apr 19.

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.

MeSH terms

  • Acetylcholinesterase / chemistry
  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Animals
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / isolation & purification
  • Antitubercular Agents / pharmacology*
  • Butyrylcholinesterase / chemistry*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / isolation & purification
  • Cholinesterase Inhibitors / pharmacology*
  • Electrophorus
  • Horses
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / isolation & purification
  • Indole Alkaloids / pharmacology*
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / growth & development
  • Oxazines
  • Pentacyclic Triterpenes / isolation & purification
  • Pentacyclic Triterpenes / pharmacology
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Spiro Compounds / chemistry
  • Spiro Compounds / isolation & purification
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship
  • Voacanga / chemistry*
  • Xanthenes

Substances

  • Alkaloids
  • Antitubercular Agents
  • Cholinesterase Inhibitors
  • Indole Alkaloids
  • Oxazines
  • Pentacyclic Triterpenes
  • Plant Extracts
  • Spiro Compounds
  • Xanthenes
  • deoxyvobtusine
  • globospiramine
  • resazurin
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • lupeol