RESUMEN
The biotransformation of huperzine B (hupB), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. One new compound, 8α,15α-epoxyhuperzine B (1), along with two known oxygenated hupB analogs, 16-hydroxyhuperzine B (2) and carinatumin B (3), was isolated and identified. The structures of all the isolates were deduced by spectroscopic methods including NMR, MS, IR, and UV spectra. The known compounds 2 and 3 were obtained from a microbial source for the first time. To the best of our knowledge, it is the first report on the microbial transformation of hupB and would facilitate further structural modification of hupB by chemo-enzymatic method. In the LPS-induced neuro-inflammation injury assay, 8α,15α-epoxyhuperzine B (1) exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with an EC50 of 40.1â nm.
Asunto(s)
Alcaloides/química , Huperzia/química , Alcaloides/metabolismo , Alcaloides/farmacología , Biotransformación , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Huperzia/metabolismo , Lipopolisacáridos/toxicidad , Conformación Molecular , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Plantas Medicinales/química , Plantas Medicinales/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/farmacologíaRESUMEN
The biotransformation of huperzine A (hupA), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. Two previously undescribed compounds 1-2, along with a known analog 8α,15α-epoxyhuperzine A (3), were isolated and identified. The structures of all the isolates were established by spectroscopic methods including NMR, MS, IR, and UV spectra. In particular, the absolute configurations of 1 and 2 were elucidated by CD spectra comparison and theoretic NOE strength calculation. In the LPS-induced neuro-inflammation injury assay, 1-3 exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with EC50 values of 35.3⯱â¯0.9, 32.1⯱â¯0.9, and 50.3⯱â¯0.8â¯nM, respectively.