ABSTRACT
Chemical investigation into the culture broth of the plant endophyte Penicillium sp. HS-11 in the modified Martin's medium supplemented with subemylanilide hydroxamic acid (SAHA), a well-known histone deacetylase (HDACs) inhibitor, led to the isolation and identification of two induced products 4-epipenicillone B (1) and (R)-(+)-chrysogine (2). 4-epipenicillone B (1) was obtained as a new compound whose structure was elucidated by comprehensive spectroscopic methods including 1 D/2D NMR, HRESMS, and quantum chemistry calculations including DFT GIAO 13C NMR and ECD calculation. Acquisition of 4-epipenicillone B (1) enriched the chemical diversities of fungal natural products possessing a tricyclo [5.3.1.03,8] undecane skeleton. The cytotoxic activity of 1 was also evaluated.
Subject(s)
Penicillium , Polyketides , Epigenesis, Genetic , Epigenomics , Penicillium/chemistry , Penicillium/isolation & purification , Polyketides/chemistry , Polyketides/pharmacologyABSTRACT
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.
Subject(s)
Alkaloids/metabolism , Huperzia/microbiology , Polyporales/metabolism , Sesquiterpenes/metabolism , Biotransformation , Cell Line, Tumor , China , Endophytes/metabolism , Humans , Huperzia/chemistry , Neuroprotective Agents , Phytochemicals/metabolism , Plants, Medicinal/chemistry , Plants, Medicinal/microbiologyABSTRACT
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.
