Synthesis, Antifungal Activities and Molecular Docking Studies of Benzoxazole and Benzothiazole Derivatives

Based on benzoxazole and benzothiazole scaffold as an important pharmacophore, two series of 2-(aryloxymethyl) benzoxazole and benzothiazole derivatives were synthesized and their antifungal effects against eight phytopathogenic fungi were evaluated. Compounds 5a, 5b, 5h, and 5i exhibited significant antifungal activities against most of the pathogens tested. Especially 5a, 5b, 5h, 5i, 5j, and 6h inhibited the growth of F. solani with IC(50) of 4.34–17.61 μg/mL, which were stronger than that of the positive control, hymexazol (IC(50) of 38.92 μg/mL). 5h was the most potent inhibitor (IC(50) of 4.34 μg/mL) against F. Solani, which was about nine times more potent than hymexazol. Most of the test compounds displayed significant antifungal effects against B. cinerea (IC(50) of 19.92–77.41 μg/mL), among them, 5a was the best one (IC(50) of 19.92 μg/mL). The structure-activity relationships (SARs) were compared and analyzed. The result indicates that the electron-drawing ability and position of the substituents have a significant impact on biological activities. Furthermore, docking studies were carried out on the lipid transfer protein sec14p from S. cerevisiae, and preliminarily verified the antifungal activities. Taken together, these results provide 2-(phenoxymethyl)benzo[d]oxazole as an encouraging framework that could lead to the development of potent novel antifungal agents.