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Bioorg Med Chem Lett ; 30(17): 127407, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32738992

RESUMEN

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.


Asunto(s)
Fármacos Neuroprotectores/química , Triterpenos Pentacíclicos/química , Animales , Bacillus megaterium/química , Bacillus megaterium/metabolismo , Biotransformación , Supervivencia Celular/efectos de los fármacos , Cobalto/toxicidad , Hidroxilación , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacología , Oxidación-Reducción , Células PC12 , Triterpenos Pentacíclicos/síntesis química , Triterpenos Pentacíclicos/metabolismo , Triterpenos Pentacíclicos/farmacología , Ratas , Ácido Betulínico
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