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

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)-beta-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.

Automated summary

Phytochemical investigation of Woodfordia fruticosa flowers led to the identification of flavonoids with anti-SmltD activity, with compound 1 showing the most potent inhibition. Further study revealed compound 1 exerted competitive inhibition with respect to ATP, providing a foundation for the development of novel SmltD inhibitors.