Design and Synthesis of Mandelic Acid Derivatives for Suppression of Virulence via T3SS against Citrus Canker.

Citrus canker, a highly contagious bacterial disease caused by Xanthomonas citri subsp. citri (Xcc), poses a substantial threat to citrus crops, leading to serious reductions in fruit yield and economic losses. Most commonly used bactericides against Xcc lead to the rapid development of resistant subpopulations. Therefore, it is imperative to create novel drugs, such as type III secretion system (T3SS) inhibitors, that specifically target bacterial virulence factors rather than bacterial viability. In our study, we designed and synthesized a series of mandelic acid derivatives including 2-mercapto-1,3,4-thiazole. Seven substances were found to reduce the level of transcription of hpa1 without affecting bacterial viability. In vivo bioassays indicated that compound F9 significantly inhibited hypersensitive response and pathogenicity. RT-qPCR assays showed that compound F9 visibly suppressed the expression of Xcc T3SS-related genes as well as citrus canker susceptibility gene CsLOB1. Furthermore, the combination with compound F9 and quorum-quenching bacteria HN-8 can also obviously alleviate canker symptoms.

Novel mandelic acid derivatives suppress virulence of Ralstonia solanacearum via type III secretion system.

BACKGROUND: Bacterial 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. RESULTS: In 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. CONCULSION: The 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.

Design, Synthesis, In Vitro Antifungal Activity and Mechanism Study of the Novel 4-Substituted Mandelic Acid Derivatives.

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.

Synthesis, Antifungal Evaluation, 3D-QSAR, and Preliminarily Mechanism Study of Novel Chiral Mandelic Acid Derivatives.

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' (EC50 = 19.3 µg/mL) against Gibberella saubinetii, which was approximately 16 times higher than that of H3 (EC50 = 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.

The interplays among meteorology, source, and chemistry in high particulate matter pollution episodes in urban Shanghai, China.

High particulate matter (PM) pollution episodes still occur occasionally in urban China, despite of improvements in recent years. Investigating the influencing factors of high-PM episodes is beneficial in the formulation of effective control measures. We herein present the effects of weather condition, emission source, and chemical conversion on the occurrence of high-PM episodes in urban Shanghai using multiple online measurements. Three high-PM episodes, i.e., locally-accumulated, regionally-transported, and dust-affected ones, as well as a clean period were selected. Stagnant air with temperature inversion was found in both locally-accumulated and regionally-transported high-PM episodes, but differences in PM evolution were observed. In the more complicated dust-affected episode, the weather condition interacted with the emission/transport sources and chemical conversion, resulting in consecutive stages with different PM characteristics. Specifically, there were (1) stronger local accumulation in the pre-dust period, (2) dust-laden air with aged organic aerosol (OA) upon dust arrival, (3) pollutants being swept into the ocean, and (4) back to the city with aged OA. Our results suggest that (a) local emissions could be rapidly oxidized in some episodes but not all, (b) aged OA from long-range transport (aged in space) had a similar degree of oxygenation compared to the prolonged local oxidation (aged in time), and (c) OA aged over land and over the ocean were similar in chemical characteristics. The findings help better understand the causes and evolution of high-PM episodes, which are manifested by the interplays among meteorology, source, and chemistry, providing a scientific basis for control measures.

Application of transport timescales to coastal environmental assessment: a case study.

A numerical model based on the random walk particle tracking technique is developed to simulate the transport of the contaminants discharged into the coastal area of Guangxi, China from rivers. The model couples a 1D river flow module and a 2D coastal circulation module. Two transport timescales, i.e., the age and the arrival time, are introduced to characterize the contaminant transport process. The age is the time for a particle taken to enter the domain of interest after it left the place where the age is initially set to zero. The arrival time, on the other hand, is the age of the particle arriving at a particular place most quickly after release. It is useful for emergency responses to such an accident as toxic substance leakage. By the numerical model, the age and the arrival time under various conditions in the coastal area of Guangxi, China are studied in details. The age distribution and the arrival time of particles at a specific location are shown to closely rely on the coastal hydrodynamic environment in addition to the distance of the location from the source where particles are released. Particles released at spring tide and at ebb tide are found to spread more quickly than those released at neap tide and at flood tide, respectively. A large carrying discharge of river reduces the ages of the contaminants from the river concerned when transported to a place within the coastal area, while it has less influence on the arrival time, particularly in a place along the coast.