Thiodiazole Copper Research Articles

Activity-based protein profiling guided new target identification of quinazoline derivatives for expediting bactericide discovery: Activity-based protein profiling derived new target discovery of antibacterial quinazolines

IntroductionThe looming antibiotic-resistance problem has imposed an enormous crisis on global public health and agricultural development. Even worse, the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens have made the resurgence of diseases that were once easily treatable deadly again. The development of antibiotics with novel mechanisms of action is urgently required. ObjectivesInspired by charming activity-based protein profiling (ABPP) technology and increasing attention to quinazolines in the development of antibacterial agents, this study engineered a series of new quinazoline derivatives, assessed their antibacterial profiles, and first identified the possible target. MethodsThe target identification and their possible binding sites were verified by ABPP technology, molecular docking, and molecular dynamic simulations. The fatty acid synthesis process was analyzed by gas chromatography, propidium iodide staining, and scanning electron microscopy. The physicochemical properties and fungicide-likeness were evaluated using the Fungicide Physicochemical-properties Analysis Database. ResultsCompound 7a, an acrylamide-functionalized quinazoline derivative, exhibited excellent antibacterial potency against Xanthomonas oryzae pv. oryzae with an EC50 value of 13.20 µM. More importantly, ABPP technology showed that β-ketoacyl-ACP-synthase Ⅱ (FabF) was the first identified quinazolines’ potential target. Compound 7a could selectively bind to the Cys151 residue of FabF through covalent interaction, suppress fatty acid biosynthesis, and damage the cell membrane integrity, thereby killing the bacteria. The pot experiment results showed that compound 7a demonstrated protective and curative values of 49.55 % and 47.46 %, surpassing controls bismerthiazol and thiodiazole copper. Finally, compound 7a exhibited low toxicity towards non-target organisms. These unprecedented performances contributed to excavating new quinazoline-based bactericidal agents. ConclusionOur research highlights the superiority of ABPP technology, for the first time, identifies the target of engineered quinazolines in pathogenic bacteria, and their potential target fished by ABPP tools holds great promise for the development of quinazoline-based and/or FabF-targeted bactericides.

Synthesis and Biological Evaluation of Novel Coumarin Derivatives Bearing a Sulfonamide Moiety as Antiviral and Antibacterial Agent

AbstractTwenty novel 4-bromocoumarin derivatives bearing a sulfonamide moiety were designed and synthesized. Their antiviral and antibacterial activities were systematically evaluated. The test results show that all the target compounds possess moderate to excellent antiviral and antibacterial activities. Among all target compounds, one compound exhibited good antiviral activity against TMV, CMV, and PVY, which is superior to ribavirin. Moreover, two target compounds exhibited good in vitro antibacterial activity against Psa, with an EC50 value of 44.9 mg/L and 49.3 mg/L, respectively, which were better than thiodiazole copper and zinc thiazole, with an EC50 value of 56.3 mg/L and 50.2 mg/L, respectively. The results provide insights for the development of multifunctional pesticides.

Novel trans-Resveratrol Derivatives: Design, Synthesis, Antibacterial Activity, and Mechanisms.

Rice bacterial leaf blight and rice bacterial leaf streak have induced tremendous damage to production of rice worldwide. To discover an effective novel antibacterial agent, a series of novel trans-resveratrol (RSV) derivatives containing 1,3,4-oxadiazole and amide moieties were designed and synthesized for the first time. Most of them showed excellent antibacterial activities against Xanthomonas oryzae pv oryzicola and Xanthomonas oryzae pv oryzae. Especially, compound J12 had the best inhibitory with the half-maximal effective concentration values of 4.2 and 5.0 mg/L, respectively, which were better than that of RSV (63.7 and 75.4 mg/L), bismerthiazol (79.5 and 89.6 mg/L), and thiodiazole copper (105.4 and 112.8 mg/L). Furthermore, compound J12 had an excellent control effect against rice bacterial leaf streak and rice bacterial leaf blight, with protective activities of 46.2 and 42.1% and curative activities of 44.5 and 41.7%, respectively. Preliminary mechanisms indicated that compound J12 could not only remarkably decrease biofilm formation, extracellular polysaccharide production, and the synthesis of extracellular enzymes but also destroy bacterial cell surface morphology, thereby reducing the pathogenicity of bacteria. In addition, compound J12 could increase the activity of defense-related enzymes and affect the expression of multiple pathogenic-related genes including plant-pathogen interaction, the MAPK signaling pathway, and phenylpropanoid biosynthesis, and this could improve the defense of rice against rice bacterial leaf streak infection. The present work indicates that the RSV derivatives can be used as promising candidates for the development of antibacterial agents.

Design, synthesis, antimicrobial activity, and mechanism of novel 3-(2,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives.

Plant pathogens cause substantial crop losses annually, posing a grave threat to global food security. Fungicides have usually been used for their control, but the rapid development of pesticide resistance renders many ineffective, therefore the search for novel and efficient green pesticides to prevent and control plant diseases has become the top priority in crop planting. The results of bioassay studies indicated that most of the target compounds showed certain antimicrobial activity in vitro. In particular, compound X7 showed high inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC50 value of 27.47 μg mL-1, surpassing conventional control agents such as thiazole zinc (41.55 μg mL-1) and thiodiazole copper (53.39 μg mL-1). Further studies on molecular docking showed that X7 had a strong binding affinity with 2FBW. The morphological change observed by scanning electron microscopy indicated that the surface of Xoo appears wrinkled and cracked under X7 treatment and a total of 2662 proteins were identified by label-free proteomic analysis. Three experiments have elucidated the mechanism whereby X7 induced considerable changes in the physiological and biochemical properties of Xoo, which in turn affected the reproduction and growth of bacteria. This work represents a pivotal advancement, offering important reference for the research and development therapeutics in combating plant pathogens. © 2024 Society of Chemical Industry.

Discovery of a novel series of phenylthiazole thioether (sulfone) compounds based on natural thiasporine A as potential candidates for controlling rice fungal and bacterial diseases

AbstractHalf of the world's population depends on rice for their calories. Protecting rice in the growth period from damage caused by phytopathogens is faced with a great challenge under the frequent extreme climate. To find novel fungicides to control rice diseases, 35 novel phenylthiazole‐1,3,4‐oxadiazole‐thioether (sulfone) derivatives were synthesized and evaluated for their efficacy against destructive fungal and bacterial diseases of rice. Bioassay results demonstrated that most of G‐series compounds possessed excellent antifungal and antibacterial activities. In particular, compounds G1 (EC50 = 2.22 μg/mL, R.s) and G7 (EC50 = 2.76 μg/mL, R.s) showed the most promising antifungal activities in vitro and exhibited superior protective and curative activities against rice sheath blight in vivo compared with commercial carbendazim. Surprisingly, compound G2 exhibited the remarkable antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) with an EC50 value of 1.98 μg/mL, and demonstrated superior protective activity (88.08%) than thiodiazole copper (79.39%) against rice bacterial leaf blight at 200 μg/mL. The abovementioned results fully manifested that the phenylthiazole‐1,3,4‐oxadiazole‐sulfone structure, especially compounds G1 and G2, had the potential to develop as commercial agents for controlling rice fungal and bacterial diseases.

Synthesis and agricultural antimicrobial evaluation of new quinazoline derivatives containing both a piperazine linker and the N-acetyl moiety.

To discover more efficient agricultural antimicrobial agents, a series of new quinazoline derivatives containing both a piperazine linker and the N-acetyl moiety were prepared and assessed for their antibacterial and antifungal activities. All the target compounds were characterized by 1H and 13C NMR as well as high-resolution mass spectrometry (HRMS), and the chemical structure of the most potent compound E19 incorporating a 4-trifluoromethoxy substituent was clearly confirmed via single crystal X-ray diffraction measurements. The bioassay results indicated that some compounds possessed notable inhibitory effects in vitro against the bacterium Xanthomonas oryzae pv. oryzicola (Xoc). For example, compound E19 had an EC50 (effective concentration for 50% activity) value of 7.1 μg/mL towards this pathogen, approximately 15- and 10-fold more effective than the commercial bactericides thiodiazole copper and bismerthiazol (EC50 = 110.2 and 72.4 μg/mL, respectively). Subsequently, the mechanistic studies showed that compound E19 likely exerted its antibacterial efficacies by altering the cell morphology, increasing the permeability of bacterial cytoplasmic membrane, suppressing the production of bacterial extracellular polysaccharides and the extracellular enzyme activities (amylase and cellulase), and blocking the swimming motility of Xoc. Moreover, the proteomic analysis revealed that compound E19 could reduce the bacterial flagellar biosynthesis and decrease the flagellar motility by down-regulating the expression of the related differential proteins. Compound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry.

Novel aurone-derived piperazine sulfonamides: Development and mechanisms of action as immunostimulants against plant bacterial diseases

Bacterial diseases pose a significant threat to the sustainable production of crops. Given the unsatisfactory performance and poor eco-compatibility of conventional bactericides, here we present a series of newly structured bactericides that are inspiringly designed by aurone found in plants of the Asteraceae family. These aurone-derived compounds contain piperazine sulfonamide motifs and have shown promising in vitro performance against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola and Xanthomonas axonopodis pv. citri, in particular, compound II23 achieved minimum half-maximal effective concentrations of 1.06, 0.89, and 1.78 μg/mL, respectively. In vivo experiments conducted in a greenhouse environment further revealed that II23 offers substantial protective and curative effects ranging between 68.93 and 70.29% for rice bacterial leaf streak and 53.17–64.43% for citrus bacterial canker, which stands in activity compared with lead compound aurone and commercial thiodiazole copper. Additional physiological and biochemical analyses, coupled with transcriptomics, have verified that II23 enhances defense enzyme activities and chlorophyll levels in rice. Significantly, it also stimulates the accumulation of abscisic acid (ABA) and upregulates the expression of key genes OsPYL/RCAR5, OsBIPP2C1, and OsABF1, thereby activating the ABA signaling pathway in rice plants under biological stress from bacterial infections.

Rational design, synthesis, and antimicrobial evaluation of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety.

In this paper, a series of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety were constructed. The synthetic compounds were characterized by 1H NMR, 13C NMR, HRMS, and single crystal diffraction. The antimicrobial activities of title compounds against fungi (Pyricutaria oryzae Cav., Phomopsis sp., Botryosphaeria dothidea, cucumber Botrytis cinerea, tobacco Botrytis cinerea, blueberry Botrytis cinerea) and bacteria (Xanthomonas oryzae pv. oryzicola, Xoc; Xanthomonas axonopodis pv. citri, Xac) revealed these compounds possessed excellent antibacterial activity through mycelial growth rate method and turbidity method, respectively. Among them, compounds 7a, 7d, 7g, 7k, 7l, and 7n had the antibacterial inhibition rate of 90.68, 97.86, 93.61, 97.70, 97.26, and 92.34%, respectively. The EC50 values of 7a, 7d, 7g, 7k, 7l, and 7n were 58.31, 48.76, 58.50, 40.11, 38.15, and 46.99μg/mL, separately, superior to that of positive control pesticide thiodiazole copper (104.26μg/mL). The molecular docking simulation of compound 7l and glutathione s-transferase also confirmed its good activity. The in vivo bioassay toward Xac infected citrus leaves was also performed to evaluate the potential of compounds as efficient antibacterial reagent. Further study of antibacterial mechanism was also carried out, including extracellular polysaccharide production, permeability of bacterial membrane, and scanning electron microscope observations. The excellent antibacterial activities of these compounds provided a strong support for its application for preventing and control plant diseases.

Synthesis, Structural Characterization, and Biological Activities of 1,3,4- Thiadiazole Derivatives Containing Sulfonylpiperazine Structures.

To develop novel bacterial biofilm inhibiting agents, a series of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures were designed, synthesized, and characterized using 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. Meanwhile, their biological activities were evaluated, and the ensuing structure-activity relationships were discussed. The bioassay results showed the substantial antimicrobial efficacy exhibited by most of the compounds. Among them, compound A24 demonstrated a strong efficacy with an EC50 value of 7.8 μg/mL in vitro against the Xanthomonas oryzae pv. oryzicola (Xoc) pathogen, surpassing commercial agents thiodiazole copper (31.8 μg/mL) and bismerthiazol (43.3 μg/mL). Mechanistic investigations into its anti-Xoc properties revealed that compound A24 operates by increasing the permeability of bacterial cell membranes, inhibiting biofilm formation and cell motility, and inducing morphological changes in bacterial cells. Importantly, in vivo tests showed its excellent protective and curative effects on rice bacterial leaf streak. Besides, molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are key factors between the binding of A24 and AvrRxo1-ORF1. Therefore, these results suggest the utilization of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures as a bacterial biofilm inhibiting agent, warranting further exploration in the realm of agrochemical development.

Unlocking nature's potential: Novel isomagnolone analogues as broad-spectrum antimicrobial agents for plant disease control

In an effort to develop novel, less toxic, and effective controls for plant diseases, we aimed to identify derivatives of the natural product isomagnolone with antimicrobial activity. We established a facile method for the synthesis of isomagnolone and its isomer Ⅱ, and prepared a series of novel isomagnolone analogues bearing N-(1,3-thiazol-2-yl)amides Ⅲ1–30. The structures of Ⅲ1–30 were determined by IR, 1H NMR, 13C NMR, and ESI-MS. Among them, compounds Ⅲ24 and Ⅲ26 exhibited potent antifungal activity against four fungi with EC50 values substantially lower than that of the positive control, hymexazol. Additionally, the antibacterial results showed that Ⅲ20 and Ⅲ22 displayed more potent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) with EC50 values of 12.6 and 10.3 ​μg/mL, respectively, approximately 2-fold lower than that of the positive control, thiodiazole copper (EC50: 24.0 ​μg/mL). Structure-activity relationships suggested that the antifungal activity of title isomagnolone analogues was favored when the substituent (R) was pyridyl or the 2-chloro-3-pyridyl group. Mechanism of action studies revealed that Ⅲ22 could disrupt bacterial membranes, thus resulting in cell death. Furthermore, the potent compounds Ⅲ20, Ⅲ22, Ⅲ24, and Ⅲ26 showed low toxicity against the human hepatocyte cell line (LO2). Given these results, these isomagnolone analogues bearing N-(1,3-thiazol-2-yl)amides are promising antimicrobials against phytopathogenic fungi and bacteria for controlling plant diseases.

Design and Enantioselective Synthesis of Chiral Pyranone Fused Indole Derivatives with Antibacterial Activities against Xanthomonas oryzae pv oryzae for Protection of Rice.

A new class of chiral pyranone fused indole derivatives were prepared by means of N-heterocyclic carbene (NHC) organocatalysis and demonstrated notable antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo). Bioassays showed that compounds (3S,4R)-5b, (3S,4R)-5d, and (3S,4R)-5l exhibited promising in vitro efficacy against Xoo, with EC50 values of 9.05, 9.71, and 5.84 mg/L, respectively, which were superior to that of the positive controls with commercial antibacterial agents, bismerthiazol (BT, EC50 = 27.8 mg/L) and thiodiazole copper (TC, EC50 = 70.1 mg/L). Furthermore, single enantiomer (3S,4R)-5l was identified as an optimal structure displaying 55.3% and 52.0% curative and protective activities against Xoo in vivo tests at a concentration of 200 mg/L, which slightly surpassed the positive control with TC (curative and protective activities of 47.2% and 48.8%, respectively). Mechanistic studies through molecular docking analysis revealed preliminary insights into the distinct anti-Xoo activity of the two single enantiomers (3S,4R)-5l and (3R,4S)-5l, wherein the (3S,4R)-configured stereoisomer could form a more stable interaction with XooDHPS (dihydropteroate synthase). These findings underscore the significant anti-Xoo potential of these chiral pyranone fused indole derivatives, and shall inspire further exploration as promising lead structures for a novel class of bactericides to combat bacterial infections and other plant diseases.

Design, synthesis, antibacterial evaluation of isopropylamine linked with different substituted phenol and piperazine novel derivatives.

Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 μg mL-1) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.

Design, synthesis and antibacterial activity of quinazolinone derivatives containing glycosides

A series of novel quinazolinone derivatives containing glycosides were designed and synthesized. The biological activities test found that this series of compounds had good antibacterial activities. Among all target compounds, compounds 1 and 15 showed good antibacterial activity in vitro against Pseudomonas syringae pv. actinidiae (Psa), with an EC50 value of 48.7 mg/L, 45.6 mg/L, respectively, which better than thiodiazole copper (54.6 mg/L) and zinc thiazole (49.2 mg/L). Compounds 15 and 23 showed good in vitro antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) at a concentration of 100 mg/L, with inhibition rates of 79.3% and 77.1%, respectively, which better than thiodiazole copper (71.8%). In addition, compound 15 can cause significant deformation of cell surface.

Design, Synthesis, Antibacterial, and Antifungal Evaluation of Phenylthiazole Derivatives Containing a 1,3,4-Thiadiazole Thione Moiety.

To effectively control the infection of plant pathogens, we designed and synthesized a series of phenylthiazole derivatives containing a 1,3,4-thiadiazole thione moiety and screened for their antibacterial potencies against Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, as well as their antifungal potencies against Sclerotinia sclerotiorum, Rhizoctonia solani, Magnaporthe oryzae and Colletotrichum gloeosporioides. The chemical structures of the target compounds were characterized by 1H NMR, 13C NMR and HRMS. The bioassay results revealed that all the tested compounds exhibited moderate-to-excellent antibacterial and antifungal activities against six plant pathogens. Especially, compound 5k possessed the most remarkable antibacterial activity against R. solanacearum (EC50 = 2.23 μg/mL), which was significantly superior to that of compound E1 (EC50 = 69.87 μg/mL) and the commercial agent Thiodiazole copper (EC50 = 52.01 μg/mL). Meanwhile, compound 5b displayed the most excellent antifungal activity against S. sclerotiorum (EC50 = 0.51 μg/mL), which was equivalent to that of the commercial fungicide Carbendazim (EC50 = 0.57 μg/mL). The preliminary structure-activity relationship (SAR) results suggested that introducing an electron-withdrawing group at the meta-position and ortho-position of the benzene ring could endow the final structure with remarkable antibacterial and antifungal activity, respectively. The current results indicated that these compounds were capable of serving as promising lead compounds.

Synthesis, biological evaluation, and molecular docking of novel ferulic acid derivatives containing a 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.

In this study, 24 novel ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine were designed and synthesized. Bioactivity assay showed that some of the target compounds exhibited moderate to good antifungal activity against Botryosphaeria dothidea BD), Phomopsis sp. (PS), Botrytis cinerea (BC), Fusarium spp. (FS), Fusarium graminearum (FG), and Colletotrichum sp. (CS). Especially, compound 6f demonstrated superior antifungal activity against Phomopsis sp., with an EC50 value of 12.64 μg mL-1, outperforming pyrimethanil (35.16 μg mL-1) and hymexazol (27.01 μg mL-1). Meanwhile, compound 6p showed strong antibacterial activity against X. axonopodis pv. citri (XAC) in vitro, with an inhibition ratio of 85.76%, which was higher than thiodiazole copper's 76.59% at 100 μg mL-1. Furthermore, molecular docking simulations elucidated that compound 6f engaged in hydrogen bonding with the succinate dehydrogenase (SDH) enzyme at SER-17, SER-39, ARG-14 and ARG-43 sites, clarifying its mode of action. This study highlights the potential of these novel ferulic acid derivatives as promising agents for controlling fungal and bacterial threats to plant health. To the best of our knowledge, this study represents the first report on the antifungal and antibacterial properties of ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.

Bactericidal bissulfone B7 targets bacterial pyruvate kinase to impair bacterial biology and pathogenicity in plants.

The prevention and control of rice bacterial leaf blight (BLB) disease has not yet been achieved due to the lack of effective agrochemicals and available targets. Herein, we develop a series of novel bissulfones and a novel target with a unique mechanism to address this challenge. The developed bissulfones can control Xanthomonas oryzae pv. oryzae (Xoo), and 2-(bis(methylsulfonyl)methylene)-N-(4-chlorophenyl) hydrazine-1-carboxamide (B7) is more effective than the commercial drugs thiodiazole copper (TC) and bismerthiazol (BT). Pyruvate kinase (PYK) in Xoo has been identified for the first time as the target protein of our bissulfone B7. PYK modulates bacterial virulence via a CRP-like protein (Clp)/two-component system regulatory protein (regR) axis. The elucidation of this pathway facilitates the use of B7 to reduce PYK expression at the transcriptional level, block PYK activity at the protein level, and impair the interaction within the PYK-Clp-regR complex via competitive inhibition, thereby attenuating bacterial biology and pathogenicity. This study offers insights into the molecular and mechanistic aspects underlying anti-Xoo strategies that target PYK. We believe that these valuable discoveries will be used for bacterial disease control in the future.

Discovery of tryptanthrin analogues bearing F and piperazine moieties as novel phytopathogenic antibacterial and antiviral agents.

Plant bacterial infections and plant viruses seriously affect the yield and quality of crops. Based on the various activities of tryptanthrin, a series of tryptanthrin analogues bearing F and piperazine moieties were designed, synthesized, and evaluated for their biological activities against three plant bacteria and tobacco mosaic virus (TMV). Bioassay results indicated that compounds 6a-6l displayed excellent antibacterial activities in vitro and 6a-6c and 6g exhibited better antiviral activities against TMV than commercial ribavirin. In particular, 6b showed the most effect on Xanthomonas oryzae pv. oryzae (Xoo) with a half-maximal effective concentration (EC50 ) of 1.26 μg mL-1 , compared with the commercial pesticide bismerthiazol (BT; EC50 = 34.3 μg mL-1 ) and thiodiazole copper (TC; EC50 = 73.3 μg mL-1 ). Meanwhile, 6a also had the best antiviral activity at 500 μg mL-1 for curative, protection, and inactivation purposes, compared with ribavirin in vivo. Compound 6b could cause changes in bacterial morphology, induce the accumulation of reactive oxygen species, promote apoptosis of bacterial cells, inhibit the formation of biofilm, and block the growth of Xoo cells. Proteomic analysis revealed major differences in the bacterial secretory system pathways T2SS and T6SS, which inhibited membrane transport. Molecular docking revealed that 6a and 6g could interact with TMV coat protein preventing virus assembly. These results suggest that tryptanthrin analogues bearing F and piperazine moieties could be promising candidate agents for antibacterial and antiviral use in agricultural production. © 2023 Society of Chemical Industry.

Design, synthesis, and bioactivity studies of chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine

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.

Repurposing Salicylamides to Combat Phytopathogenic Bacteria and Induce Plant Defense Responses.

Based on the research strategy of "drug repurposing", a series of derivatives and marketed drugs that containing salicylic acid skeleton were tested for their antibacterial activities against phytopathogens. Salicylic acid can not only regulate some important growth metabolism of plants, but also induce plant disease resistance. The bioassay results showed that the salicylamides exhibited excellent antibacterial activity. Especially, oxyclozanide showed the best antibacterial effect against Xanthomonas oryzae, Xanthomonas axonopodis pv. citri and Pectobacterium atroseptica with MICs of 0.78, 3.12 and 12.5 μg.mL-1, respectively. In vivo experiments with rice bacterial leaf blight had further demonstrated that oxyclozanide exhibited stronger antibacterial activity than the commercial bactericide, thiodiazole copper. Oxyclozanide could induce plant defense responses through the determination of salicylic acid content and the activities of defense-related enzymes including CAT, POD, and SOD in rice. The preliminarily antibacterial mechanism study indicated that oxyclozanide exhibited the antibacterial activity by disrupting cell integrity and reducing bacterial pathogenicity. Additionally, oxyclozanide could induce plant defense responses through the determination of salicylic acid content.

Design, synthesis, antibacterial and antiviral evaluation of chalcone derivatives containing benzoxazole

In this study, 24 chalcone derivatives containing benzoxazole were designed and synthesized, and the structures of all target compounds were confirmed by NMR and HRMS. The results of antibacterial activity showed that the median effective concentration (EC50) value of Z2 against Xanthomonas oryzae pv.oryzae (Xoo) was 8.10 μg/mL, which was better than thiodiazole copper (60.62 μg/mL), the antibacterial activity of Z2 was verified by scanning electron microscopy (SEM). Antibacterial mechanism of Z2 on Xoo was preliminarily explored, and the results showed concentrations were 100, 50 mg/L, which had a good cell membrane permeability to Xoo and can inhibit the EPS content and the production of extracellular enzymes, affecting the formation of biofilm, preliminary validation of the antibacterial effect of Z2 on Xoo. At 200 mg/L, Z2 had a better protective activity on harvested potatoes, which was comparable with thiodiazole copper. The activity against tobacco mosaic virus (TMV) was determined with half leaf dry spot method. The EC50 value of curative activity of Z15 was 101.97 μg/mL, which was superior to ningnanmycin (NNM) 294.27 μg/mL, and the EC50 value of protective activity of Z16 was 104.05 μg/mL, which was superior to NNM 185.73 μg/mL. Molecular docking results showed Z15, Z16 had a significantly higher affinity with tobacco mosaic virus coat protein (TMV-CP) than NNM. The above results indicated that chalcone derivatives containing benzoxazole have the potential to become antibacterial and antivirial agents.