Synthesis and Evaluation of Antifungal Activity of Novel Potent SDHI Fungicides Featuring a Conjugated Alkyne Structural Motif

Abstract

The productivity and quality of agricultural commodities are significantly affected by plant pathogenic fungi, thereby necessitating the urgent development of new fungicides with specific structures, high efficacy, and low toxicity. In this study, a series of novel conjugated alkynes as succinate dehydrogenase inhibitors were synthesized, and their antifungal properties were evaluated. The bioassay results demonstrated that most synthesized compounds exhibited greater potency against Rhizoctonia solani than other fungal species. Specifically, compounds 4 and 16 exhibited remarkable in vitro inhibitory effects against Rhizoctonia solani, with EC 50 values of 0.05 and 0.20 μmol/L, respectively. This signifies a noteworthy enhancement compared to the control Boscalid, which exhibited an EC 50 value of 1.55 μmol/L. Moreover, compound 16 demonstrated a relatively broad-spectrum antifungal activity against five additional pathogenic fungi and exhibited in vivo protective effects on rapeseed leaves and tomato fruit. Notably, the succinate dehydrogenase inhibitory activities revealed that compounds 16 and 22 displayed a stronger inhibitory effect on porcine succinate dehydrogenase (SDH) with IC 50 values of 1.85 and 0.39 μmol/L, respectively, compared to Fluxapyroxad (IC 50 = 5.48 μmol/L). Molecular docking and DFT calculations have confirmed that the binding mode of compound 16 closely resembles that of Fluxapyroxad. Incorporating a conjugated alkyne motif in these compounds can enhance their binding affinity with the target protein, thereby providing a valuable structural design strategy for further developing succinate dehydrogenase inhibitors.