Novel flavonol derivatives containing benzoxazole as potential antiviral agents: design, synthesis, and biological evaluation.

A series of flavonol derivatives containing benzoxazole were designed and synthesized, and the structures of all the target compounds were determined by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The structure of X2 was further confirmed by single crystal X-ray diffraction analysis. The results of the bioactivity tests showed that some of the target compounds possessed excellent antiviral activity against tobacco mosaic virus (TMV) in vivo. In particular, the median effective concentration (EC50) values for the curative and protective activities of X17 against TMV were 127.6 and 101.2 µg/mL, respectively, which were superior to those of ningnanmycin (320.0 and 234.6 µg/mL). The results of preliminary mechanism study indicated that X17 had a strong binding affinity for TMV coat protein (TMV-CP), which might hinder the self-assembly and replication of TMV particles. In addition, X17 was able to effectively inhibit tobacco leaf membrane lipid peroxidation and facilitate the removal of O2- from the body, thereby improving the disease resistance of tobacco plants. Therefore, the design and synthesis of flavonol derivatives containing benzoxazole provides value for the development of new antiviral drugs.

Research Progress on Benzimidazole Fungicides: A Review.

Benzimidazole fungicides are a class of highly effective, low-toxicity, systemic broad-spectrum fungicides developed in the 1960s and 1970s, based on the fungicidal activity of the benzimidazole ring structure. They exhibit biological activities including anticancer, antibacterial, and antiparasitic effects. Due to their particularly outstanding antibacterial properties, they are widely used in agriculture to prevent and control various plant diseases caused by fungi. The main products of benzimidazole fungicides include benomyl, carbendazim, thiabendazole, albendazole, thiophanate, thiophanate-methyl, fuberidazole, methyl (1-{[(5-cyanopentyl)amino]carbonyl}-1H-benzimidazol-2-yl) carbamate, and carbendazim salicylate. This article mainly reviews the physicochemical properties, toxicological properties, disease control efficacy, and pesticide residue and detection technologies of the aforementioned nine benzimidazole fungicides and their main metabolite (2-aminobenzimidazole). On this basis, a brief outlook on the future research directions of benzimidazole fungicides is presented.

Formononetin derivatives containing benzyl piperidine: A brand new, highly efficient inhibitor targeting Xanthomonas spp.

INTRODUCTION: Plant bacterial diseases take an incalculable toll on global food security. The indiscriminate use of chemical synthetic pesticide not only facilitates pathogen resistance of pathogenic bacteria, but also poses a major threat to human health and environmental protection. Therefore, it is of great economic value and scientific significance to develop a new antibacterial drug with environmental friendliness and unique mechanism of action. OBJECTIVES: To design and synthesize formononetin derivatives based on natural products, evaluate their in vitro and in vivo antibacterial activities and elucidate the mechanisms involved. METHODS: The synthesis was carried out by classical active group splicing method. The antibacterial activities were evaluated using turbidimetry and pot experiments. The antibacterial mechanism was further investigated using scanning electron microscopy (SEM), virulence factors, defense enzymes activities, proteomics and metabolomics. RESULTS: 40 formononetin derivatives containing benzyl piperidine were designed and synthesized. The antibacterial results demonstrated that H32 exhibited the most potent inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with the EC50 of 0.07 µg/mL, while H6 displayed the highest inhibitory activity against Xanthomonas axonopodis pv. Citri (Xac) with the EC50 of 0.24 µg/mL. Furthermore, the control efficacy of H32 against rice bacterial leaf blight (BLB) and H6 against citrus canker (CC) was validated through pot experiments. SEM, virulence factors and host enzyme activities assay indicated that H32 could not only reduce the virulence of Xoo, but also activate the activities of defense enzymes and improve the disease resistance of host plants. The proteomics and metabolomics analysis demonstrated that H32 could inhibit the synthesis of branched-chain amino acids, make Xoo cells in a starvation state, inhibit its proliferation, weaken its virulence and reduce its colonization and infection of host cells. CONCLUSION: Formononetin derivatives containing benzyl piperidine could be used as potentially effective inhibitors against Xanthomonas spp.

Synthesis, antibacterial and antifungal activity of myricetin derivatives containing piperidine and amide fragments.

BACKGROUND: Continuous use of synthetic bactericides and fungicides is causing pathogens to develop resistance, resulting in increased use of pesticides and affecting food security. The green pesticides derived from natural products could reduce or avoid 'pesticide hazards' caused by synthetic pesticides as a result of their unique mechanism of action. Therefore, it is of great significance to create green pesticides with novel structures. RESULTS: Herein, 30 novel myricetin derivatives containing piperidine and amide fragments were designed and synthesized using active group splicing. Among them, compound Z30 had excellent inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with the half effective concentration (EC50 ) of 2.7 µg mL-1 . Compound Z26 not only exhibited better antibacterial activity against Xaxonopodis pv. Citri (Xac) with EC50 of 3.9 µg mL-1 , but also displayed higher antifungal activity against Rhizoctonia solani (Rs) with EC50 of 8.3 µg mL-1 . In vivo experiments proved that Z30 against bacterial blight of rice and Z26 against rice blast exhibits significant protective and curative effect. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that Z26 and Z30 could change the integrity of cell wall and membrane of pathogen Xoo, Xac and Rs, resulting in cytoplasmic leakage and eventually death. Enzymatic assay, molecular docking and molecular dynamics simulations (MDs) indicated that Z26 could be used as a potential succinate dehydrogenase inhibitor (SDHI). CONCLUSION: Z26 and Z30 significantly reduced the pathogenicity of the pathogens, which provided a new idea and direction for the development of green pesticides. © 2023 Society of Chemical Industry.