Synthesis, Antifungal Activity and Molecular Docking Study of 1,3,4-Thiadiazole-Urea Compounds Containing gem-Dimethylcyclopropane Ring Structure

Abstract

In an attempt to search for natural renewable product-based antifungal agents, eighteen 1,3,4-thiadiazole-urea compounds containing gem-dimethylcyclopropane ring structure were designed and synthesized. The antifungal activity of the target compounds against six plant pathogens was preliminarily evaluated at the concentration of 50 mg/L. As a result, the inhibitory rates of (＋)-cis-1-(4-bromophenyl)-3-(5-((2,2-dimethyl-3-propylcyclopropyl)methyl)-1,3,4-thiadiazol-2-yl) urea (7i) against Colletotrichum orbicular, Bipolaris maydis and Alternaria solani were 91.2%, 85.0% and 60.1%, respectively, which was better than that of the positive control chlorothalonil. Furthermore, a reasonable and effective 3D-quantitative structure-activity relationship (3D-QSAR) model (r 2 ＝0.990, q 2 ＝0.517) was established by the comparative molecular field analysis method (CoMFA). The binding mode between the target compounds and succinate dehydrogenase (SDH) was investigated by molecular docking, and the cation-π interaction between the key residue Arg and the benzene ring was quantitatively analyzed. The gem-dimethylcyclopropane and thiadiazole-urea-benzene moieties of the target compounds probably made major contributions to the antifungal activity by frontier molecular orbital calculation.

Copper-Catalyzed N-Arylation of Pyranoquinolinones with Boronic Acids at Room Temperature without Ligand

“…However, compared with many commercially available fungicides, citral still has the disadvantages of low antibacterial activity, strong volatility and low chemical stability. Thus, in recent years, citral has been converted into a series of derivatives in order to afford compounds with better biological activity [5][6][7].…”