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

[Display omitted] 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...

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Published in:Bioorganic & medicinal chemistry letters 2021-03, Vol.36, p.127787-127787, Article 127787
Main Authors: Lee, Yuan-E, Kodama, Takeshi, Win, Nwet Nwet, Ki, Dae-Won, Hoang, Nhat Nam, Wong, Chin Piow, Lae, Khine Zar Wynn, Ngwe, Hla, Dairi, Tohru, Morita, Hiroyuki
Format: Article
Language:English
Subjects:
Docking simulation
Peptidoglycan
SmltD inhibitors
Steady-state enzyme kinetics
Stenotrophomonas maltophilia
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Summary:[Display omitted] 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2021.127787