Design, synthesis, and mechanism study of novel 1-arylisoquinoline derivatives as antifungal agents

Abstract

In screening for natural-based fungicides, a series of 32 novel 1-arylisoquinoline derivatives were designed, synthesized, and evaluated for their antifungal activities. Their structures were verified by 1H NMR, 13C NMR, HRMS and single X-ray crystal diffraction analysis. Most of the target products exhibited medium to excellent antifungal activity against 6 phytopathogenic fungi in vitro at a concentration of 50 mg/L. Interestingly, compounds A13 and A25 with EC50 values of 2.375, 2.251 mg/L s against A. alternate, that were similar to boscalid (EC50 = 1.195 mg/L). The in vivo experiments revealed that A13 presented 51.61% and 70.97% protection activities against A. alternate at the dosage of 50 and 100 mg/L, respectively, which were equal to that of boscalid (64.52% and 77.42%). The SEM analysis indicated that compound A13 could strongly damage the mycelium morphology. Molecular electrostatic potential and molecular docking analysis revealed that A13 was covered by negative potential contour, and strongly interacts with the residues of SDH. These results revealed that compounds A13 and A25 could be as promising antifungal candidates for the development of natural-based fungicides.