Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages

Shwu Fen Chang; Bo Hon Chou; Li Ming Yang; Feng Lin Hsu; Wen Kuang Lin; Yi Ho; Shwu Jiuan Lin

doi:10.1016/j.bmc.2009.07.029

Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages

Shwu Fen Chang, Bo Hon Chou, Li Ming Yang, Feng Lin Hsu, Wen Kuang Lin, Yi Ho, Shwu Jiuan Lin

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

Microbial transformation of isosteviol oxime (ent-16-E-hydroxyiminobeyeran-19-oic acid) (2) with Aspergillus niger BCRC 32720 and Absidia pseudocylindrospora ATCC 24169 yielded several compounds. In addition to bioconverting the d-ring to lactone and lactam moieties, 4α-carboxy-13α-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone (7) and 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam (10), one known compound, ent-1β,7α-dihydroxy-16-oxo-beyeran-19-oic acid (6), and five new compounds, ent-7α-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (3), ent-1β,7α-dihydroxy-16-E-hydroxyiminobeyeran-19-oic acid (4), ent-1β-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (5), ent-8β-cyanomethyl-13-methyl-12-podocarpen-19-oic acid (8), and ent-8β-cyanomethyl-13-methyl-13-podocarpen-19-oic acid (9), were isolated from the microbial transformation of 2. Elucidation of the structures of these isolated compounds was primarily based on 1D and 2D NMR, and HRESIMS data, and 3-5 were further confirmed by X-ray crystallographic analyses. Additionally, the inhibitory effects of all of these compounds were evaluated on NF-κB and AP-1 activation in LPS-stimulated RAW 264.7 macrophages. Among the compounds tested, 5 and 10 significantly inhibited NF-κB activation, with 5 showing equal potency to dexamethasone; 3 and 6-9 significantly inhibited AP-1 activation, particularly 8, which showed more inhibitory activity than dexamethasone.

Original language	English
Pages (from-to)	6348-6353
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2009.07.029
Publication status	Published - Sept 1 2009

Keywords

AP-1
Diterpenoid
Isosteviol oxime
Microbial transformation
NF-κB

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Organic Chemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry
Biochemistry

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10.1016/j.bmc.2009.07.029

Cite this

@article{2952a73c7ea1409a885684a0d9efda35,

title = "Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages",

abstract = "Microbial transformation of isosteviol oxime (ent-16-E-hydroxyiminobeyeran-19-oic acid) (2) with Aspergillus niger BCRC 32720 and Absidia pseudocylindrospora ATCC 24169 yielded several compounds. In addition to bioconverting the d-ring to lactone and lactam moieties, 4α-carboxy-13α-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone (7) and 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam (10), one known compound, ent-1β,7α-dihydroxy-16-oxo-beyeran-19-oic acid (6), and five new compounds, ent-7α-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (3), ent-1β,7α-dihydroxy-16-E-hydroxyiminobeyeran-19-oic acid (4), ent-1β-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (5), ent-8β-cyanomethyl-13-methyl-12-podocarpen-19-oic acid (8), and ent-8β-cyanomethyl-13-methyl-13-podocarpen-19-oic acid (9), were isolated from the microbial transformation of 2. Elucidation of the structures of these isolated compounds was primarily based on 1D and 2D NMR, and HRESIMS data, and 3-5 were further confirmed by X-ray crystallographic analyses. Additionally, the inhibitory effects of all of these compounds were evaluated on NF-κB and AP-1 activation in LPS-stimulated RAW 264.7 macrophages. Among the compounds tested, 5 and 10 significantly inhibited NF-κB activation, with 5 showing equal potency to dexamethasone; 3 and 6-9 significantly inhibited AP-1 activation, particularly 8, which showed more inhibitory activity than dexamethasone.",

keywords = "AP-1, Diterpenoid, Isosteviol oxime, Microbial transformation, NF-κB, AP-1, Diterpenoid, Isosteviol oxime, Microbial transformation, NF-κB",

author = "Chang, {Shwu Fen} and Chou, {Bo Hon} and Yang, {Li Ming} and Hsu, {Feng Lin} and Lin, {Wen Kuang} and Yi Ho and Lin, {Shwu Jiuan}",

note = "Funding Information: We thank Ms. Shou-Ling Huang for the NMR data acquisition and Mr. Yi-Hung Liu for conducting X-ray crystallography at the Instrumentation Center of National Taiwan University, Taipei, Taiwan. We also thank Dr. John P. N. Rosazza, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, for kindly providing the bacterial strains. Financial support from the National Science Council of Taiwan (NSC97-2320-B-038-009 and NSC98-2320-B-038-011-MY3) is gratefully acknowledged. ",

year = "2009",

month = sep,

day = "1",

doi = "10.1016/j.bmc.2009.07.029",

language = "English",

volume = "17",

pages = "6348--6353",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd",

number = "17",

}

TY - JOUR

T1 - Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages

AU - Chang, Shwu Fen

AU - Chou, Bo Hon

AU - Yang, Li Ming

AU - Hsu, Feng Lin

AU - Lin, Wen Kuang

AU - Ho, Yi

AU - Lin, Shwu Jiuan

N1 - Funding Information: We thank Ms. Shou-Ling Huang for the NMR data acquisition and Mr. Yi-Hung Liu for conducting X-ray crystallography at the Instrumentation Center of National Taiwan University, Taipei, Taiwan. We also thank Dr. John P. N. Rosazza, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, for kindly providing the bacterial strains. Financial support from the National Science Council of Taiwan (NSC97-2320-B-038-009 and NSC98-2320-B-038-011-MY3) is gratefully acknowledged.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Microbial transformation of isosteviol oxime (ent-16-E-hydroxyiminobeyeran-19-oic acid) (2) with Aspergillus niger BCRC 32720 and Absidia pseudocylindrospora ATCC 24169 yielded several compounds. In addition to bioconverting the d-ring to lactone and lactam moieties, 4α-carboxy-13α-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone (7) and 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam (10), one known compound, ent-1β,7α-dihydroxy-16-oxo-beyeran-19-oic acid (6), and five new compounds, ent-7α-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (3), ent-1β,7α-dihydroxy-16-E-hydroxyiminobeyeran-19-oic acid (4), ent-1β-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (5), ent-8β-cyanomethyl-13-methyl-12-podocarpen-19-oic acid (8), and ent-8β-cyanomethyl-13-methyl-13-podocarpen-19-oic acid (9), were isolated from the microbial transformation of 2. Elucidation of the structures of these isolated compounds was primarily based on 1D and 2D NMR, and HRESIMS data, and 3-5 were further confirmed by X-ray crystallographic analyses. Additionally, the inhibitory effects of all of these compounds were evaluated on NF-κB and AP-1 activation in LPS-stimulated RAW 264.7 macrophages. Among the compounds tested, 5 and 10 significantly inhibited NF-κB activation, with 5 showing equal potency to dexamethasone; 3 and 6-9 significantly inhibited AP-1 activation, particularly 8, which showed more inhibitory activity than dexamethasone.

AB - Microbial transformation of isosteviol oxime (ent-16-E-hydroxyiminobeyeran-19-oic acid) (2) with Aspergillus niger BCRC 32720 and Absidia pseudocylindrospora ATCC 24169 yielded several compounds. In addition to bioconverting the d-ring to lactone and lactam moieties, 4α-carboxy-13α-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone (7) and 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam (10), one known compound, ent-1β,7α-dihydroxy-16-oxo-beyeran-19-oic acid (6), and five new compounds, ent-7α-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (3), ent-1β,7α-dihydroxy-16-E-hydroxyiminobeyeran-19-oic acid (4), ent-1β-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (5), ent-8β-cyanomethyl-13-methyl-12-podocarpen-19-oic acid (8), and ent-8β-cyanomethyl-13-methyl-13-podocarpen-19-oic acid (9), were isolated from the microbial transformation of 2. Elucidation of the structures of these isolated compounds was primarily based on 1D and 2D NMR, and HRESIMS data, and 3-5 were further confirmed by X-ray crystallographic analyses. Additionally, the inhibitory effects of all of these compounds were evaluated on NF-κB and AP-1 activation in LPS-stimulated RAW 264.7 macrophages. Among the compounds tested, 5 and 10 significantly inhibited NF-κB activation, with 5 showing equal potency to dexamethasone; 3 and 6-9 significantly inhibited AP-1 activation, particularly 8, which showed more inhibitory activity than dexamethasone.

KW - AP-1

KW - Diterpenoid

KW - Isosteviol oxime

KW - Microbial transformation

KW - NF-κB

KW - AP-1

KW - Diterpenoid

KW - Isosteviol oxime

KW - Microbial transformation

KW - NF-κB

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U2 - 10.1016/j.bmc.2009.07.029

DO - 10.1016/j.bmc.2009.07.029

M3 - Article

C2 - 19648015

AN - SCOPUS:68649087855

SN - 0968-0896

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EP - 6353

JO - Bioorganic and Medicinal Chemistry

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ER -

Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages

Abstract

Keywords

ASJC Scopus subject areas

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CCDC 722590: Experimental Crystal Structure Determination

CCDC 722592: Experimental Crystal Structure Determination

CCDC 722591: Experimental Crystal Structure Determination

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Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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Fingerprint

Datasets

CCDC 722590: Experimental Crystal Structure Determination

CCDC 722592: Experimental Crystal Structure Determination

CCDC 722591: Experimental Crystal Structure Determination

Cite this