Evaluation of the antibacterial activity of diverse coumarin [3,4]-fused tetrahydroheterocycles

Abstract

Three novel classes of coumarin [3,4]-fused tetrahydroheterocyclics were synthesized in one step using donor-acceptor cyclopropane diesters as 1,3-dipoles via a facile [3 + 2]/[3 + 3] annulation/lactonization strategies. The antibacterial activities of these compounds were evaluated against two species of animal-derived pathogenic bacteria (Staphylococcus aureus, Escherichia coli) and three species of plant-derived pathogenic bacteria (Xanthomonas citri, Pseudomonas oryzae, Fusarium oxysporum). The results showed that coumarin-fused tetrahydrofuran compounds (e.g., 3aa, 3ac and 3ae) exhibited significant selective antibacterial activity against Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 2 μg/mL, while no obvious inhibitory effect was observed against other tested strains. Coumarin-fused tetrahydropyridazines (e.g., 7ad, 7ae, 7ah and 7ag) displayed excellent antibacterial activity against Pseudomonas oryzae and Fusarium oxysporum, with an MIC value of 2 μg/mL for all, and their antibacterial effect was significantly superior to that of osthol (the positive control). In contrast, coumarin-fused tetrahydro-1,2-oxazines showed relatively weak antibacterial activity, only compounds 5 ac and 5ak exerted moderate inhibitory effects on Staphylococcus aureus and Pseudomonas oryzae, both with an MIC value of 4 μg/mL. The findings of this study provide an important theoretical basis for the design and synthesis of novel coumarin-fused tetrahydroheterocyclic antibacterial agents.