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Bioorg Med Chem Lett ; 30(17): 127407, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32738992

ABSTRACT

In this study, seven 30-norlupane derivatives (2-8) wasobtained from the chemical oxidation ofbetulinic acidfollowed bybiotransformationviaBacillus megateriumCGMCC 1.1741. And metabolites 2-4 and 6-8 were newly identified products. In the first step, betulinic acid was chemically oxidizedto platanic acid (1). Following the chemical oxidation, B. megaterium catalyzed the hydroxylation at C-7, C-11, C-15 and C-23 of platanic acid (1) as well as the oxidation of C-3 hydroxyl group. Compared to the labor-intensive isolation from natural plants, this chemical-microbial semi-synthesis is more capable to provide increased structural diversity of oxygenated 30-norlupane. Finally, the potential neuroprotective effect of the derivatives was assessed on neuron-like PC12 cells induced by cobalt chloride (CoCl2). Metabolite 6 showed a potent neuroprotective activity.


Subject(s)
Neuroprotective Agents/chemistry , Pentacyclic Triterpenes/chemistry , Animals , Bacillus megaterium/chemistry , Bacillus megaterium/metabolism , Biotransformation , Cell Survival/drug effects , Cobalt/toxicity , Hydroxylation , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , Oxidation-Reduction , PC12 Cells , Pentacyclic Triterpenes/chemical synthesis , Pentacyclic Triterpenes/metabolism , Pentacyclic Triterpenes/pharmacology , Rats , Betulinic Acid
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