Plant pathogenic fungi could cause significant losses to agricultural productions. To discover new pesticides with novel structures and unique mechanisms of action, a series of novel acetophenone derivatives containing 1,3,4-thiadiazole-2-thioethers...

To investigate the effect of spatial configuration on the biological activity of the compounds, a series of chiral mandelic acid derivatives with a moiety of 1,3,4-oxadiazole thioether have been designed and synthesized. Bioassay results demonstrated that most title compounds with the S-configuration exhibited better in vitro antifungal activity against three plant fungi, such as H3′ (EC 50 = 19.3 μg/mL) against Gibberella saubinetii, which was approximately 16 times higher than that of H3 (EC 50 = 317.0 μg/mL). CoMFA and CoMSIA models were established for 3D-QSAR analysis and provided an important support for further optimization of this series of compounds. Comparing the preliminary mechanism studies between enantiomers (H3 and H3′) found that the S-configuration compound (H3′) exhibited a stronger ability to destroy the surface structure of G. saubinetii mycelia, causing the leakage of intracellular substances to accelerate and the growth of the hyphae to be inhibited. The results provided a novel view for the further optimization of this series of active compounds and deep mechanism study of chiral pesticides.

BACKGROUNDBacterial wilt induced by Ralstonia solanacearum is regarded as one of the most devastating diseases. However, excessive and repeated use of the same bactericides has resulted in development of bacterial resistance. Targeting bacterial virulence factors, such as type III secretion system (T3SS), without inhibiting bacterial growth is a possible assay to discover new antimicrobial agents.RESULTSIn this work, identifying new T3SS inhibitors, a series of mandelic acid derivatives with 2‐mercapto‐1,3,4‐thiazole moiety was synthesized. One of them, F‐24, inhibited the transcription of hrpY gene significantly. The presence of this compound obviously attenuated hypersensitive response (HR) without inhibiting bacterial growth of R. solanacearum. The transcription levels of those typical T3SS genes were reduced to various degrees. The test of the ability of F‐24 in protecting plants demonstrated that F‐24 protected tomato plants against bacterial wilt without restricting the multiplication of R. solanacearum. The mechanism of this T3SS inhibition is through the PhcR‐PhcA‐PrhG‐HrpB pathway.CONCULSIONThe screened F‐24 could inhibit R. solanacearum T3SS and showed better inhibitory activity than previously reported inhibitors without affecting the growth of the strain, and F‐24 is a compound with good potential in the control of R. solanacearum. © 2023 Society of Chemical Industry.

No abstract

Plant diseases caused by phytopathogenic fungi are a serious threat in the process of crop production and cause large economic losses to global agriculture. To obtain high-antifungal-activity compounds with novel action mechanisms, a series of 4-substituted mandelic acid derivatives containing a 1,3,4-oxadiazole moiety were designed and synthesized. In vitro bioassay results revealed that some compounds exhibited excellent activity against the tested fungi. Among them, the EC50 values of E13 against Gibberella saubinetii (G. saubinetii), E6 against Verticillium dahlia (V. dahlia), and E18 against Sclerotinia sclerotiorum (S. sclerotiorum) were 20.4, 12.7, and 8.0 mg/L, respectively, which were highly superior to that of the commercialized fungicide mandipropamid. The morphological studies of G. saubinetii with a fluorescence microscope (FM) and scanning electron microscope (SEM) indicated that E13 broke the surface of the hyphae and destroyed cell membrane integrity with increased concentration, thereby inhibiting fungal reproduction. Further cytoplasmic content leakage determination results showed a dramatic increase of the nucleic acid and protein concentrations in mycelia with E13 treatment, which also indicated that the title compound E13 could destroy cell membrane integrity and affect the growth of fungi. These results provide important information for further study of the mechanism of action of mandelic acid derivatives and their structural derivatization.