Rational understanding of chiral fungicide penthiopyrad stereoselectivity: Bioactivity, aquatic toxicity and cytotoxicity

Penthiopyrad is a novel chiral succinate dehydrogenase inhibitor (SDHI) fungicide with two enantiomers. However, enantioselective information on the biological activity, nontarget organisms and human health risk of penthiopyrad is not comprehensive, which may cause inaccurate risk assessment. In this study, the enantioselective bioactivity to three kinds of phytopathogens (Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum) was first disclosed, and the antifungal activity of S-(+)-penthiopyrad was higher than that of R(-)-penthiopyrad by 12-37 times. Moreover, its enantioselective toxicity to Raphidocelis subcapitata and Daphnia magna was also clarified, and the order of toxicity was S-(+)-penthiopyrad > rac-penthiopyrad >R-(-)-penthiopyrad, with 1.8- and 5.3-fold differences between the two enantiomers. Furthermore, the enantioselectivity of penthiopyrad on HepG2 cytotoxicity was studied. The data showed that the cytotoxicity of S-(+)-penthiopyrad was 1.8 times higher than that of R-(-)-penthiopyrad, and S-(+)-penthiopyrad had a stronger impact on cell proliferation, oxidative stress and lipid peroxidation. In summary, due to the enantioselectivity of the activity and toxicity of the chiral pesticide, the efficacy and risk evaluation of penthiopyrad should be considered at the enantiomer level.