Pyrazolo[3,4-c]isothiazole and isothiazolo[4,3-d]isoxazolederivatives as antifungal agents

Context: The diseases of plants and humans due to pathogenic fungi are increasing. Among the substances used tocombat fungi, the azoles are of primary interest, both in agricultural field both in health. To avoid fungal resistancephenomena, the synthesis and tests of new derivatives are necessary.Objective: This article discusses the synthesis and the antifungal activity of pyrazolo[3,4-c]isothiazole andisothiazolo[4,3-d]isoxazole derivatives against three fungi that are pathogenic only for plants and two fungi that areopportunistic in humans and plants.Materials and Methods: The compounds were prepared starting from 2-cyano-3-ethoxy-2-butenethioamide. Theantifungal activity of the compounds was determined by measuring the inhibition of growth of the fungi tested at20, 50, and 100 μg/mL in comparison with the controls.Results: Results demonstrated that several compounds were able to control the mycelial growth of the tested fungi,even if they showed different sensitivity to the different azole-derivatives. In general Magnaporthe grisea (T.T. Hebert)Yaegashi & Udagawa was the most sensitive fungus, being blocked almost entirely by 4-chloro derivative even at 20μg/mL, a concentration at which the reference commercial compound tricyclazole was nearly ineffective.Discussion and conclusion: These findings demonstrate that the pyrazolo[3,4-c]isothiazole derivatives have a widespectrum of activity on phytopathogenic and opportunistic fungi. In particular the 4-chloro derivative seems to havea great potential as new product to combat M. grisea in the agricultural field.