Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan

Yuan E. Lee; Takeshi Kodama; Nwet Nwet Win; Dae Won Ki; Nhat Nam Hoang; Chin Piow Wong; Khine Zar Wynn Lae; Hla Ngwe; Tohru Dairi; Hiroyuki Morita

doi:10.1016/j.bmcl.2021.127787

Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan

Yuan E. Lee, Takeshi Kodama, Nwet Nwet Win, Dae Won Ki, Nhat Nam Hoang, Chin Piow Wong, Khine Zar Wynn Lae, Hla Ngwe, Tohru Dairi^*, Hiroyuki Morita

^*Corresponding author for this work

Section of Natural Products & Drug Discovery, Division of Medicinal Resources, Institute of Natural Medicine

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

1 Scopus citations

Abstract

SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-L-Ala and L-Glu to form UDP-MurNAc-L-Ala-L-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6′′-galloyl)-β-D-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.

Original language	English
Article number	127787
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	36
DOIs	https://doi.org/10.1016/j.bmcl.2021.127787
State	Published - 2021/03/15

Keywords

Docking simulation
Peptidoglycan
SmltD inhibitors
Steady-state enzyme kinetics
Stenotrophomonas maltophilia

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2021.127787

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@article{8b2308de88f741ca9e265e0cd671f507,

title = "Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan",

abstract = "SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-L-Ala and L-Glu to form UDP-MurNAc-L-Ala-L-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6′′-galloyl)-β-D-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.",

keywords = "Docking simulation, Peptidoglycan, SmltD inhibitors, Steady-state enzyme kinetics, Stenotrophomonas maltophilia",

author = "Lee, {Yuan E.} and Takeshi Kodama and Win, {Nwet Nwet} and Ki, {Dae Won} and Hoang, {Nhat Nam} and Wong, {Chin Piow} and Lae, {Khine Zar Wynn} and Hla Ngwe and Tohru Dairi and Hiroyuki Morita",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = mar,

day = "15",

doi = "10.1016/j.bmcl.2021.127787",

language = "英語",

volume = "36",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

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TY - JOUR

T1 - Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan

AU - Lee, Yuan E.

AU - Kodama, Takeshi

AU - Win, Nwet Nwet

AU - Ki, Dae Won

AU - Hoang, Nhat Nam

AU - Wong, Chin Piow

AU - Lae, Khine Zar Wynn

AU - Ngwe, Hla

AU - Dairi, Tohru

AU - Morita, Hiroyuki

PY - 2021/3/15

Y1 - 2021/3/15

N2 - SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-L-Ala and L-Glu to form UDP-MurNAc-L-Ala-L-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6′′-galloyl)-β-D-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.

AB - SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-L-Ala and L-Glu to form UDP-MurNAc-L-Ala-L-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6′′-galloyl)-β-D-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.

KW - Docking simulation

KW - Peptidoglycan

KW - SmltD inhibitors

KW - Steady-state enzyme kinetics

KW - Stenotrophomonas maltophilia

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U2 - 10.1016/j.bmcl.2021.127787

DO - 10.1016/j.bmcl.2021.127787

M3 - 学術論文

C2 - 33460740

AN - SCOPUS:85099711410

SN - 0960-894X

VL - 36

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

M1 - 127787

ER -

Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan

Abstract

Keywords

ASJC Scopus subject areas

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