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Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
by
Wu, Jingwan
, Zhou, Dongdong
, Wen, Zhenchang
, Wei, Chengwen
, Feng, Zhao
, Xu, Jing
, Zhang, Xuexia
, Feng, Ting
in
Calcineurin
/ CaN/NFAT signaling pathway
/ Cell activation
/ chemical structure
/ Concanavalin A
/ cytochalasins
/ Dephosphorylation
/ Diaporthe
/ Drugs
/ Endophytes
/ Enzymes
/ Fungi
/ immunosuppression
/ immunosuppressive activity
/ Immunosuppressive agents
/ Interleukin 2
/ Lipopolysaccharides
/ lymphocyte proliferation
/ Lymphocytes
/ mangrove endophytic fungi
/ Mangroves
/ Metabolites
/ Natural products
/ NF-AT protein
/ NF-AT1 protein
/ NMR
/ Nuclear magnetic resonance
/ Phomopsis asparagi
/ Phomopsis sp
/ Proliferation
/ Signal transduction
/ Spleen
/ Toxicity
/ Transcription
/ Translocation
2022
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Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
by
Wu, Jingwan
, Zhou, Dongdong
, Wen, Zhenchang
, Wei, Chengwen
, Feng, Zhao
, Xu, Jing
, Zhang, Xuexia
, Feng, Ting
in
Calcineurin
/ CaN/NFAT signaling pathway
/ Cell activation
/ chemical structure
/ Concanavalin A
/ cytochalasins
/ Dephosphorylation
/ Diaporthe
/ Drugs
/ Endophytes
/ Enzymes
/ Fungi
/ immunosuppression
/ immunosuppressive activity
/ Immunosuppressive agents
/ Interleukin 2
/ Lipopolysaccharides
/ lymphocyte proliferation
/ Lymphocytes
/ mangrove endophytic fungi
/ Mangroves
/ Metabolites
/ Natural products
/ NF-AT protein
/ NF-AT1 protein
/ NMR
/ Nuclear magnetic resonance
/ Phomopsis asparagi
/ Phomopsis sp
/ Proliferation
/ Signal transduction
/ Spleen
/ Toxicity
/ Transcription
/ Translocation
2022
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Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
by
Wu, Jingwan
, Zhou, Dongdong
, Wen, Zhenchang
, Wei, Chengwen
, Feng, Zhao
, Xu, Jing
, Zhang, Xuexia
, Feng, Ting
in
Calcineurin
/ CaN/NFAT signaling pathway
/ Cell activation
/ chemical structure
/ Concanavalin A
/ cytochalasins
/ Dephosphorylation
/ Diaporthe
/ Drugs
/ Endophytes
/ Enzymes
/ Fungi
/ immunosuppression
/ immunosuppressive activity
/ Immunosuppressive agents
/ Interleukin 2
/ Lipopolysaccharides
/ lymphocyte proliferation
/ Lymphocytes
/ mangrove endophytic fungi
/ Mangroves
/ Metabolites
/ Natural products
/ NF-AT protein
/ NF-AT1 protein
/ NMR
/ Nuclear magnetic resonance
/ Phomopsis asparagi
/ Phomopsis sp
/ Proliferation
/ Signal transduction
/ Spleen
/ Toxicity
/ Transcription
/ Translocation
2022
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Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
Journal Article
Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
2022
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Overview
Three new cytochalasins, phomoparagins A-C (1–3), along with five known analogs (4–8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4–6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.
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