Design, Synthesis, and Structure–Activity Relationship of Quinazolinone Derivatives as Potential Fungicides

Abstract

Plant diseases caused by phytopathogenic fungi reduce the yield and quality of crops. To develop novel antifungal agents, we designed and synthesized eight series of quinazolinone derivatives and evaluated their anti-phytopathogenic fungal activity. The bioassay results revealed that compounds KZL-15, KZL-22, 5b, 6b, 6c, 8e, and 8f exhibited remarkable antifungal activity in vitro. Especially, compound 6c displayed the highest bioactivity against Sclerotinia sclerotiorum, Pellicularia sasakii, Fusarium graminearum, and Fusarium oxysporum, displaying appreciable IC50 values (50% inhibitory concentration) of 2.46, 2.94, 6.03, and 11.9 μg/mL, respectively. A further mechanism interrogation revealed abnormal mycelia, damaged organelles, and changed permeability of cell membranes in S. sclerotiorum treated with compound 6c. In addition, the in vivo bioassay indicated that compound 6c possessed comparable curative and protective effects (87.3 and 90.7%, respectively) to the positive control azoxystrobin (89.5 and 91.2%, respectively) at 100 μg/mL concentration against S. sclerotiorum. This work validated the potential of compound 6c as a new and promising fungicide candidate, contributing to the exploration of potent antifungal agents.

Design, synthesis, and bioassay of novel 1‐(3‐chloropyridin‐2‐yl)‐5‐amino‐4‐pyrazole derivatives containing a 1,3,4‐thiadiazole thioether or sulfone moiety

“…The mycelial growth inhibition method [26] was used to test the fungicidal activities of title compounds 5a – 5t and 6a – 6n against G. zeae , F. oxysporum , and C. mandshurica at a concentration of 100 μg/ml. DMSO (1%) in sterile distilled water was used as a blank control (CK).…”

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments

“…Susceptible cole leaves collected from Guizhou Academy of Agricultural Sciences were used to determine the in vivo efficacy of F15 according to previous literature [50,51]. Leaves that were of uniform size and similar shape were resected from healthy rapeseed plants, which were sterilized with 1% sodium hypochlorite for 1 min, and they were then rinsed with sterilized water and were blotted with sterile filter paper.…”

“…SEM observations of the hyphae of S. sclerotiorum were implemented in line with reported methods [51,54]. Mycelium disks with a diameter of 5 mm were taken from the edge of PDA medium containing 50 µg/mL of F15 and were incubated for 2 days at 25 • C, and PDA with 0.1% MDF was used as a control.…”

“…A molecular docking station was built using the Ledock program according to the literature [14,51]. At present, due to the lack of reports on the tri-dimensional structures of the SDH of the fungal species, the crystal structure of SDH (PDB ID: 2FBW) [14,21,48] was downloaded from Gallus gallus on the Protein Data Bank (https://www.rcsb.org, las accessed on 18 October 2021) and was processed with Pymol.…”

“…To vividly explain the interaction mechanism and the binding stability between compound F15 or fluopyram and SDH, MDS was performed to revise the docking results, and Gromacs software (version 2020.5) was used for the MD simulations [41,51,58]. The force fields of these two compounds were obtained at https://www.bio2byte.be/research/, last accessed on 18 October 2021), and water was then added under the stand of the compound "amber96sb.ff".…”