Discovery of γ-Lactam Alkaloid Derivatives as Potential Fungicidal Agents Targeting Steroid Biosynthesis

Abstract

Biological control of plant pathogens is considered as one of the green and effective technologies using beneficial microorganisms or microbial secondary metabolites against plant diseases, and so microbial natural products have played important roles in the research and development of new and green agrochemicals. To explore the potential applications for natural γ-lactam alkaloids and their derivatives, 26 γ-lactams that have flexible substituent patterns were synthesized and characterized, and their in vitro antifungal activities against eight kinds of plant pathogens belonging to oomycetes, basidiomycetes, and deuteromycetes were fully evaluated. In addition, the high potential compounds were further tested using an in vivo assay against Phytophthora blight of pepper to verify a practical application for controlling oomycete diseases. The potential modes of action for compound D1 against Phytophthora capsici were also investigated using microscopic technology (optical microscopy, scanning electron microscopy, and transmission electron microscopy) and label-free quantitative proteomics analysis. The results demonstrated that compound D1 may be a potential novel fungicidal agent against oomycete diseases (EC50 = 4.9748 μg·mL–1 for P. capsici and EC50 = 5.1602 μg·mL–1 for Pythium aphanidermatum) that can act on steroid biosynthesis, which can provide a certain theoretical basis for the development of natural lactam derivatives as potential antifungal agents.

Application of proteomics to determine the mechanism of ozone on sweet cherries (Prunus avium L.) by time-series analysis

“…In this study, This pathways (arginine and proline metabolism, aminoacyl-tRNA biosynthesis, protein processing in endoplasmic reticulum, protein export, nucleocytoplasmic transport, proteasome) related to DEPs belong to animo acid biosynthesis, translation, and folding, sorting and degradation. The final product of biological function is protein, and amino acids are a class of crucial natural molecules for building a variety of diverse peptides and proteins, which can also take part in the formation of metabolites in organisms ( Huang et al., 2020 ; Huang et al., 2021 ). When plants are in a stress environment, in order to better adapt to this environment, amino acids in cells will respond to a certain extent.…”

Discovery of Novel Quinazoline-2-Aminothiazole Hybrids Containing a 4-Piperidinylamide Linker as Potential Fungicides against the Phytopathogenic Fungus Rhizoctonia solani

“…Plant pathogenic fungi are the most destructive plant parasitic organisms and cause enormous economic losses in global agricultural production every year, − which endanger a wide variety of crops, fruits, and vegetables. More seriously, some fungal strains are able to produce the mycotoxins, posing a severe threat to food safety and human health. , Rice sheath blight disease caused by the fungus Rhizoctonia solani is regarded as the most devastating rice disease in the world, ranking second only to rice blast .…”

Design, Synthesis, and Cytotoxic Activity of Novel Natural Arylsulfonamide-Inspired Molecules

“…Accordingly, structural optimization and derivation of natural products becomes a powerful strategy for improving the efficiency and success rate of NP-based drug development. Our research group has committed to discovering highly active compounds from natural products [ 21 , 22 , 23 , 24 , 25 , 26 ], so the rare natural product sargassulfamide A, bearing a privileged scaffold of arylsulfonamide, aroused our interest. It is well known that molecular skeletons determine whether molecules have bioactivity; despite the natural arylsulfonamide sargassulfamide A being less effective against the human cancer cell lines, we wondered whether we could modulate or improve the activities of these analogues of natural products by changing the position of the amide unit and pharmacophore hybridization.…”