Design, synthesis and anti-plant-bacterial (Xoc, Xac, Psa) activity of coumarins derivatives containing amide and sulfonamide moieties

Abstract

In this study, coumarin derivatives containing amide and sulfanilamide moieties were designed and synthesized, and their antibacterial activities were systematically evaluated. Among the synthesised compounds, compound A7 exhibited good inhibitory activity against Psa, with an EC₅₀ value of 59.4 mg/L. Compound A2 presented the most potent antibacterial effect against Xoc, with an EC₅₀ value of 43.2 mg/L. Compound A3 showed notable efficacy against Xac, with an EC₅₀ value of 53.2 mg/L. Further mechanistic studies involving scanning electron microscopy (SEM) and extracellular conductivity (EC) measurements revealed that A2 induced morphological deformation and alterations in membrane permeability alterations in Xoc cells, suggesting a potential disruption of bacterial membrane integrity. Additionally, the structure-activity relationship (SAR) of these derivatives was elucidated using 3D-QSAR model, providing insights for further structural optimization. Furthermore, the chemical reactivity of potential bioactive compounds was evaluated using density functional theory (DFT).

Keywords: Amide; Anti-Psa activity; Anti-Xac activity; Anti-Xoc activity; Anti-plant-bacterial activity; Coumarins; Heterocyclic of natural products; Sulfanilamide.

Scheme 1

Synthesis route of target compounds A1-A16

Fig. 1

The impact of compound A2 on cell morphology. Without treating (A), Treated with 50 mg/L A2 (B). Treated with 100 mg/L A2 (C)

Fig. 2

The effect of compound A2 on the permeability of Xoc membranes

Fig. 3

Linear diagrams of the experimental and predicted pEC₅₀ of the CoMFA and CoMSlA models

Fig. 4

3D contour maps of CoMFA model, electrostatic contours (A) and steric contours (B). 3D contour maps of ComSIA model, electrostatic contours (C), steric contours (D), Hydrophobic (E), hydrogen-bond donor (F) and hydrogen-bond acceptor (G)

Fig. 5

ESP diagram of compound A2