Design, Synthesis and in Vitro Antifungal Mechanism of Novel Phenylalanine Derivatives

Abstract

To explore novel molecules with unique mechanisms against plant pathogenic fungi, a series of phenylalanine derivatives containing a 1,3,4‐oxadiazothioether moiety were designed and synthesized. Bioassays revealed that some target compounds at 100 μg/mL exhibited excellent antifungal activities against Thanatephorus cucumeris, such as G6 (92.1 %), G10 (94.3 %), G18 (99.1 %), and G19 (98.7 %), better than that of the commercial fungicide azoxystrobin (90.6 %), and the EC50 value of G10 against T. cucumeris was 31.9 μg/mL. Further mechanism studies of T. cucumeris treated with G10 demonstrated that this compound can affect the growth of mycelia by disrupting the integrity of the membrane, and the higher the concentration of the compound is, the greater the degree of membrane integrity damage, similar to the commercial fungicide azoxystrobin. These conclusions provide important information for further mechanism studies of this series of phenylalanine derivatives.

Design, Synthesis, and Bioactivity of Eighteen Novel 2H‐1,4‐Benzoxazin‐3(4H)‐one Containing a Propanolamine Moiety

“…In Vitro Antifungal Activity Evaluation [36] The in vitro inhibitory activities of 2a-2l and 3a-3f against P. trachicarpicola, C. camelliae, F. oxysporum, G. zeae and T. cucumeris were determined using the mycelial growth rate method at 100 μg/mL. Experimental details and EC 50 calculation methods are included in the Supporting Information.…”

Design, Synthesis, and Target Identification of Novel Phenylalanine Derivatives by Drug Affinity Responsive Target Stability (DARTS) in Xanthomonas oryzae pv Oryzae

“…Some amino acid derivatives containing the active group of “1,3,4-oxadiazole” with superior activity against plant fungi and bacterium have been reported previously, , which prompts us to develop more novel amino acid derivatives as potential substitutes for antimicrobial agents. As another crucial component, the acylhydrazone group is always observable in existing pesticide chemicals, such as benquinox and diflufenzopyr. , To develop higher active antibacterial compounds, a series of novel dl -phenylalanine (PHE) arylhydrazone dithioether derivatives were designed and synthesized by replacing “1,3,4-oxadiazole” with the active group “acylhydrazone” on the basis of previous oxadiazole thioethers (Figure B).…”

“…26,27 Consequently, there exists a critical necessity to develop novel antibacterial agents that possess distinct modes of action (MOAs) to deal with these problems. Some amino acid derivatives containing the active group of "1,3,4-oxadiazole" with superior activity against plant fungi and bacterium have been reported previously, 28,29 component, the acylhydrazone group is always observable in existing pesticide chemicals, such as benquinox and diflufenzopyr. 30,31 To develop higher active antibacterial compounds, a series of novel DL-phenylalanine (PHE) arylhydrazone dithioether derivatives were designed and synthesized by replacing "1,3,4-oxadiazole" with the active group "acylhydrazone" on the basis of previous oxadiazole thioethers (Figure 1B).…”