BACKGROUND: Traditional pesticides have poor-water solubility, high toxicity and low bioavailability. Therefore, it is of great significance for the sustainable and healthy development of the pesticide industry to develop efficient and ecofriendly new chemical pesticide products and formulations.
OBJECTIVE: This study aims to synthesize a series of derivatives based on chalcone structure (HPPO), and then use the amphiphilic and self-assembly characteristics of N-succinyl-chitosan (NSCS) to prepare HPPO@NSCS nanoparticles (HPPO@NSCS NPs) in order to realize the green application of HPPO, and investigate the antifungal activity and mechanisms of HPPO@NSCS NPs.
METHODS: NSCS was synthesized by structural modification using chitosan as the carrier. Based on its amphiphilic and self-assembly characteristics, HPPO-16@NSCS NPs were reasonably prepared by combining with active small molecule HPPO-16. Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy (FS) and high-performance liquid chromatography (HPLC) were used to characterize the physicochemical properties of NSCS and HPPO-16@NSCS NPs. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. The mechanism of antifungal action was discussed from the observation of pathogen morphology, fluorescence staining and enzyme activity determination.
RESULTS: 28 small molecules based on chalcone structure (HPPO-1-28), NSCS and HPPO-16@NSCS were successfully synthesized. The application of HPPO-16@NSCS could impair the development, cell structure, cellular energy utilization, and metabolism pathways of the fungi. The protective effects of HPPO-16@NSCS NPs on rice leaves and leaf sheaths were 80.9 and 76.1 %, respectively, which were better than those of azoxystrobin.
CONCLUSIONS: This study reveals that these simple chalcone derivatives can be further explored as viable antibacterial alternatives and NSCS as a novel pesticide matrix can be used for the delivery of more insoluble pesticides.

Chalcone (1,3-diaryl-2-propen-1-one) is an α, β-unsaturated ketone that serves as an active constituent or precursor of numerous natural substances, exhibiting a broad spectrum of pharmacological effects. In this study, the classical Claisen-Schmidt condensation method was used to synthesize the chalcone derivative 2\',4\'-dimethoxychalcone (DTC) and evaluate its pharmacological activity. By upregulating the expression of the epithelial cell marker E-cadherin and downregulating the expression of the mesenchymal cell marker vimentin, DTC was found to inhibit transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) process in A549 cells, maintaining the cells\' epithelial-like morphology and reducing the ability of the cells to migrate. Additionally, DTC demonstrated the ability to decrease the expression levels of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in RAW264.7 cells, suggesting a possible anti-inflammatory effect. Furthermore, DTC was found to exhibit bacteriostatic activity against Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans (C. albicans), indicating that this chemical may possess broad-spectrum antibacterial activity.

Acute lung injury (ALI) is a highly heterogeneous clinical syndrome and an important cause of mortality in critically ill patients, with limited treatment options currently available. Chalcone, an essential secondary metabolite found in edible or medicinal plants, exhibits good antioxidant activity and simple structure for easy synthesis. In our study, we synthesized a novel chalcone derivative, compound 27 (C27). We hypothesized that C27 could be a potential treatment for acute respiratory distress syndrome (ARDS). Therefore, the protective effects of C27 on lung epithelial cells during ALI and the underlying molecular mechanisms were investigated. In vivo, Intratracheal instillation of LPS (10 mg/kg) was used to induce acute lung injury in mice. In vitro, the bronchial epithelial cell line (Beas-2b) was treated with 30 μM tert-butyl hydroperoxide (t-BHP) to simulate oxidative stress. Our findings demonstrate that pretreatment with C27 reduces LPS-induced oxidative destruction and cellular apoptosis in lung tissues of mice. Furthermore, it significantly attenuates t-BHP-induced cellular reactive oxygen species (ROS) generation, mitochondrial damage, and apoptosis in vitro. Mechanistically, the signaling pathway involving Nrf2-Keap1 and the downstream antioxidative proteins were activated by C27 in vivo. Additionally, PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 abolished the effect of C27 in vitro, indicating that the protective effect of C27 is mediated via the PI3K/AKT/Nrf2-Keap1 pathway. Our study provides evidence that C27 protects against LPS-induced ALI by mitigating oxidative stress via activation of the PI3K/AKT/Nrf2-Keap1 signaling pathway. Therefore, we hypothesize that C27 represents a viable alternative for ALI therapy.

24 chalcone derivatives containing 1,3,4-thiadiazole were synthesized. The results of bioactivity tests indicated that some of the target compounds exhibited superior antifungal activities in vitro. Notably, the EC50 value of D4 was 14.4 μg/mL against Phomopsis sp, which was significantly better than that of azoxystrobin (32.2 μg/mL) and fluopyram (54.2 μg/mL). The in vivo protective activity of D4 against Phomopsis sp on kiwifruit (71.2 %) was significantly superior to azoxystrobin (62.8 %) at 200 μg/mL. The in vivo protective activities of D4 were 74.4 and 57.6 % against Rhizoctonia solani on rice leaf sheaths and rice leaves, respectively, which were slightly better than those of azoxystrobin (72.1 and 49.2 %) at 200 μg/mL. Scanning electron microscopy (SEM) results showed that the mycelial surface collapsed, contracted and grew abnormally after D4 treatment. Finally, the results were further verified by in vivo antifungal assay, fluorescence microscopy (FM) observation, determination of relative conductivity, membrane lipid peroxidation degree assay, and determination of cytoplasmic content leakage. Molecular docking results suggested that D4 could be a potential SDHI.

In this study, 30 chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine were designed and synthesized. The results of antibacterial activity showed that EC50 values of N26 against Xoo, Pcb was 36.41, 38.53 μg/mL, respectively, which were better than those of thiodiazole copper, whose EC50 values were 60.62, 106.75 μg/mL, respectively. The bacterial inhibitory activity of N26 against Xoo was verified by SEM. Antibacterial mechanism between N26 and Xoo was preliminarily explored, the experimental results showed that when the drug concentration was 100 mg/L, N26 had a good cell membrane permeability of Xoo, and it can inhibit the production of EPS content and extracellular enzyme content to disrupt the integrity of the Xoo biofilms achieving the effect of inhibiting Xoo. At 200 mg/L, N26 can protect and inhibit the lesions of post-harvested potatoes in vivo. The activities of N1-N30 against TMV were determined with half leaf dry spot method. The EC50 values of the curative and protective activity of N22 was 77.64 and 81.55 μg/mL, respectively, which were superior to those of NNM (294.27, 175.88 μg/mL, respectively). MST experiments demonstrated that N22 (Kd = 0.0076 ± 0.0007 μmol/L) had a stronger binding ability with TMV-CP, which was much higher than that of NNM (Kd = 0.7372 ± 0.2138 μmol/L). Molecular docking results showed that N22 had a significantly higher affinity with TMV-CP than NNM.

Influenza viruses pose a significant threat to human health worldwide due to seasonal epidemics and occasional global pandemics. These viruses can cause severe upper respiratory tract infections that contribute to high morbidity and mortality rates. The emergence of drug-resistant influenza viruses has created the need for the development of novel broad-spectrum antivirals. Here, we present a novel anti-influenza agent with new targets and mechanisms of action to address this problem. Our findings led to the discovery of a novel influenza virus inhibitor, a ligustrazine derivative known as A9. We have found that it exhibits broad-spectrum antiviral properties against influenza A and B viruses (IAV and IBV, respectively), including oseltamivir-resistant strain. Through multiple bioassays such as time-of-addition assay, indirect immunofluorescence assay, and nuclear-cytoplasmic fractionation assay, we demonstrated that A9 inhibits the nuclear export of the viral ribonucleoprotein (vRNP). Furthermore, escape mutant analyses and affinity studies determined by surface plasmon resonance indicated that A9 specifically targets the nucleoprotein. In addition, four chalcone derivatives developed from A9 (B14, B29, B31, and B32), were found to effectively inhibit the replication of influenza virus through the same mechanism of action. In this manuscript we highlight A9 and its four derivatives as potential leads for the treatment of IAV and IBV infections, and their unique and novel mechanism of action probable benefit the field of anti-influenza drug discovery.

Histone deacetylases (HDACs) are a class of enzymes that are responsible for the removal of acetyl groups from the ε-N-acetyl lysine of histones, allowing histones to wrap DNA more tightly. HDACs play an essential role in many biological processes, such as gene regulation, transcription, cell proliferation, angiogenesis, migration, differentiation and metastasis, which make it an excellent target for anticancer drug discovery. The search for histone deacetylase inhibitors (HDACis) has been intensified, with numerous HDACis being discovered, and five of them have reached the market. However, currently available HDAC always suffers from several shortcomings, such as limited efficacy, drug resistance, and toxicity. Accordingly, dual-targeting HDACis have attracted much attention from academia to industry, and great advances have been achieved in this area. In this review, we summarize the progress on inhibitors with the capacity to concurrently inhibit tubulin polymerization and HDAC activity and their application in cancer treatment.

Generally, the potential reactive \"olefin pairs\" in the molecular crystals satisfying Schmidt\'s criteria could undergo topological [2+2] cycloaddition. In this study, another factor that affects the photodimerization reactivity of chalcone analogues was found. The cyclic chalcone analogues of (E)-2-(2,4-dichlorobenzylidene)-2,3-dihydro-1H-inden-1-one (BIO), (E)-2-(naphthalen-2-ylmethylene)-2,3-dihydro-1H-inden-1-one (NIO), (Z)-2-(2,4-dichlorobenzylidene)benzofuran-3(2H)-one (BFO), and (Z)-2-(2,4-dichlorobenzylidene)benzo[b]thiophen-3(2H)-one (BTO) have been synthesized. While the geometrical parameters for the molecular packing of the above four compounds did not exceed Schmidt\'s criteria, [2+2] cycloaddition did not occur in the crystals of BIO and BTO. The single crystal structures and Hirshfeld surface analyses revealed that interactions of C=O⋅⋅⋅H (CH2 ) existed between adjacent molecules in the crystal of BIO. Therefore, the carbonyl and methylene groups linked with one carbon atom in carbon-carbon double bond were tightly confined in the lattice, acting as a tweezer to inhibit free movement of the double bond and suppressing [2+2] cycloaddition. In the crystal of BTO, similar interactions of Cl⋅⋅⋅S and C=O⋅⋅⋅H (C6 H4 ) prevented free movement of the double bond. In contrast, the intermolecular interaction of C=O⋅⋅⋅H only exists around the carbonyl group in the crystals of BFO and NIO, leaving the C=C double bonds to move freely and allowing the occurrence of [2+2] cycloaddition. Driven by photodimerization, the needle-like crystals of BFO and NIO displayed evident photo-induced bending behavior. This work demonstrates that the intermolecular interactions around carbon-carbon double bond affect the [2+2] cycloaddition reactivity except for Schmidt\'s criteria. These findings provide valuable insights into the design of photomechanical molecular crystalline materials.

A series of 5\' monosubstituted chalcone derivatives were synthesized to explore their antitumor activity and mechanism of action in vitro. The structures of 5\' monosubstituted chalcone derivatives synthesized by reactions such as Suzuki coupling were confirmed by 1H NMR, 13C NMR and MS, and the target compounds were not reported in the literature. The antitumor activity of the aimed compounds was tested by MTT colorimetric method in vitro. Compound 5c has an IC50 value of 1.97 μM for K562 and a value of 2.23 μM for HepG2. Further investigation of the mechanism of action of compound 5c was found to have effects on K562 cell morphology, proliferation, apoptosis, cell cycle, and wound healing of HepG2 cells. The results showed that compound 5c has research value in antitumor activity and mechanism of action in vitro.

A series of novel chalcone derivatives containing pyrazole oxime ethers were designed and synthesized. The structures of all the target compounds were determined by NMR and HRMS. The structure of H5 was further confirmed via single-crystal X-ray diffraction analysis. The results of biological activity test showed that some of the target compounds exhibited significant antiviral and antibacterial activities. The test results of EC50 value against tobacco mosaic virus showed that H9 had the best curative and protective effect, and the EC50 value of curative activity of H9 was 166.9 μg/mL, which was superior to ningnanmycin (NNM) 280.4 μg/mL, the EC50 value of protective activity of H9 was 126.5 μg/mL, which was superior to ningnanmycin 227.7 μg/mL. Microscale thermophoresis (MST) experiments demonstrated that H9 (Kd = 0.0096 ± 0.0045 μmol/L) exhibited a strong binding ability with tobacco mosaic virus capsid protein (TMV-CP), which was far superior to ningnanmycin (Kd = 1.2987 ± 0.4577 μmol/L). In addition, molecular docking results showed that the affinity of H9 to TMV protein was significantly higher than ningnanmycin. The results of against bacterial activity showed that H17 has a good inhibiting effect against Xanthomonas oryzae pv. oryzae (Xoo), the EC50 value of H17 was 33.0 μg/mL, which was superior to the commercial drugs thiodiazole copper (68.1 μg/mL) and bismerthiazol (81.6 μg/mL), and the antibacterial activity of H17 was verified by scanning electron microscopy (SEM).