Novel lead compound optimization and synthesized based on the target structure of Xanthomonas oryzae pv. oryzae GlmU

• Three types of novel target compounds were optimized and synthesized.
• All of the target compounds displayed IC50 values in the 10.82–23.31 µM range, the inhibition rates were increased by 30%–67%.
• The binding mode and the possible inhibitory mechanism were analyzed by molecular docking.

Bacterial leaf blight, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases of rice worldwide. N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) was an attractive target for the development of antimicrobial agents. To develop novel, more potent and even more selective inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU (Xo-GlmU), three types of novel target compounds were optimized and synthesized based on the Xo-GlmU structure in this study. The biological testing results showed that all of the target compounds displayed the higher inhibition than the lead compound with the IC50 values in the 10.82–23.31 µM range, and the inhibition rates were increased by 30%–67%. The binding mode and the possible inhibitory mechanism of the target compounds in the active site were also analyzed by the molecular docking based on the uridyltransferase active site of Xo-GlmU.

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