Strobilurin fungicides play a crucial role in protecting plants against different pathogens and securing food supplies. A series of 1,2,3-thiadiazole and thiazole-based strobilurins were rationally designed, synthesized, characterized, and tested against various fungi. Introduction of 1,2,3-thiadiazole greatly improved the fungicidal activity of the target molecules. Compounds 8a, 8c, 8d, and 10i exhibited a relatively broad spectrum of fungicidal activity. Compound 8a showed excellent activities against Gibberella zeae, Sclerotinia sclerotiorum, and Rhizoctonia cerealis with median effective concentrations (EC) of 2.68, 0.44, and 0.01 μg/mL, respectively; it was much more active than positive controls enestroburin, kresoxim-methyl, and azoxystrobin with EC between 0.06 and 15.12 μg/mL. Comparable or better fungicidal efficacy of compound 8a compared with azoxystrobin and trifloxystrobin against Sphaerotheca fuliginea and Pseudoperonspera cubensis was validated in cucumber fields at the same application dosages. Therefore, compound 8a is a promising fungicidal candidate worthy of further development.
A molecular design approach was used in our laboratory to guide the development of imidazole-based fungicides. Based on homology modeling and molecular docking studies targeting the cytochrome P450-dependent sterol 14α-demethylase, 3,4-dichloroisothiazole-based imidazoles showed great potential. Several such compounds were then rationally designed, synthesized, characterized, and their antifungal activities were evaluated. Bioassay results showed that compounds such as ( R)-11, ( R)-12, and ( S)-11 have commendable, broad-spectrum antifungal activities that are comparable to those of commercial products. Based on Q-PCR testing and microscopy observations, the imidazole derivatives affect fungal cell wall formation through the inhibition of the BcCYP51 expression system. These findings strongly suggest that the mode of action of these imidazole compounds is similar to that of tioconazole and imazalil. This report indicates that this molecular design strategy is not only practical but productive.
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