A new selective inhibitor for IMP-1 metallo-β-lactamase, 3Z,5E-octa-3,5-diene-1,3,4-tricarboxylic acid-3,4-anhydride

3Z ,5E-Octa-3,5-diene-1,3,4-tricarboxylic acid-3,4-anhydride (ODTAA, 1) was isolated from Paecilomyces sp. FKI-6801 for its selective IMP-1 MBL inhibitory activity. The first total synthesis of 1 from the commercially available compound was achieved in 9 steps with 28% overall yield. Introduction of catechol to the maleic anhydride of 1 improved the IC50 toward IMP-1 MBL and the inhibitory activity against IMP-1 MBL-producing P. aeruginosa. Treatment of the maleic anhydride scaffold with amine showed that the beta-carbonyl-alpha,beta-unsaturated carboxylic acid moiety is required as a pharmacophore for IMP-1 MBL inhibition.

Automated summary

3Z,5E-Octa-3,5-diene-1,3,4-tricarboxylic acid-3,4-anhydride (ODTAA, 1) was isolated from Paecilomyces sp. FKI-6801 for its selective IMP-1 MBL inhibitory activity. The total synthesis of 1 was achieved from commercially available compound in 9 steps with 28% overall yield. Introduction of catechol to the maleic anhydride of 1 improved the IC50 towards IMP-1 MBL and the inhibitory activity against IMP-1 MBL-producing P. aeruginosa. Treatment of the maleic anhydride scaffold with amine revealed the beta-carbonyl-alpha,beta-unsaturated carboxylic acid moiety as a pharmacophore for IMP-1 MBL inhibition.