Structure-Based Discovery of Symmetric Disulfides from Garlic Extract as Quorum Sensing Inhibitors.

Microorganisms are the most common cause of food spoilage. is a common foodborne pathogen that causes food spoilage and poses a serious threat to food safety. As a crucial target in antitoxicity strategies, the quorum sensing (QS) system shows promising potential for further development.

Design and Synthesis of Aryl Amide Derivatives Containing Thiazole as Type III Secretion System Inhibitors against .

To identify potent inhibitors of the type III secretion system (T3SS) in the foodborne pathogen , we synthesized 35 thiazole-containing aryl amides by merging salicylic acid with various heterocycles through active splicing. Screening for promoter activity led to the discovery of a highly effective T3SS inhibitor from these 35 compounds. Through subsequent experiments, it was confirmed that compound specifically targeted the T3SS of .

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

Citrus canker, a highly contagious bacterial disease caused by subsp. (), poses a substantial threat to citrus crops, leading to serious reductions in fruit yield and economic losses. Most commonly used bactericides against lead to the rapid development of resistant subpopulations.

Discovery of novel amide derivatives as potent quorum sensing inhibitors of Pseudomonas aeruginosa.

With the increasing reports of antibiotic resistance in this species, Pseudomonas aeruginosa is a common human pathogen with important implications for public health. Bacterial quorum sensing (QS) systems are potentially broad and versatile targets for developing new antimicrobial compounds. While previous reports have demonstrated that certain amide compounds can inhibit bacterial growth, there are few reports on the specific inhibitory effects of these compounds on bacterial quorum sensing systems.

Application and Mechanism of Cryptolepine and Neocryptolepine Derivatives as T3SS Inhibitors for Control of Bacterial Leaf Blight on Rice.

Bacterial leaf blight (BLB) caused by pv oryzae () is extremely harmful to rice production. The traditional control approach is to use bactericides that target key bacterial growth factors, but the selection pressure on the pathogen makes resistant strains the dominant bacterial strains, leading to a decline in bactericidal efficacy. Type III secretion system (T3SS) is a conserved and critical virulence factor in most Gram-negative bacteria, and its expression or absence does not affect bacterial growth, rendering it an ideal target for creating drugs against Gram-negative pathogens.

Innovative Strategy for the Control of Citrus Canker: Inhibitors Targeting the Type III Secretion System of Subsp. .

To find potential type III secretion system (T3SS) inhibitors against citrus canker caused by subsp. (), a new series of 5-phenyl-2-furan carboxylic acid derivatives stitched with 2-mercapto-1,3,4-thiadiazole were designed and synthesized. Among the 30 compounds synthesized, 14 compounds significantly inhibited the promoter activity of a harpin gene Eight of the 14 compounds did not affect the growth of , but significantly reduced the hypersensitive response (HR) of tobacco and decreased the pathogenicity of on citrus plants.

Derivative of cinnamic acid inhibits T3SS of Xanthomonas oryzae pv. oryzae through the HrpG-HrpX regulatory cascade.

Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) has a significant impact on rice yield and quality worldwide. Traditionally, bactericide application has been commonly used to control this devastating disease.

A novel strategy to control Pseudomonas syringae through inhibition of type III secretion system.

Pseudomonas syringae (P. syringae) is a highly prevalent Gram-negative pathogen with over 60 pathogenic variants that cause yield losses of up to 80% in various crops. Traditional control methods mainly involve the application of antibiotics to inactivate pathogenic bacteria, but large-scale application of antibiotics has led to the development of bacterial resistance.

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.

Novel Ethyl-3-Aryl-2-Nitroacrylate Derivatives as Potential T3SS Inhibitors against pv. on Rice.

Bacterial leaf blight (BLB) caused by pv. () is a highly destructive bacterial disease. Traditional prevention methods have utilized antibiotics to target bacterial growth, which has accelerated the emergence of resistant strains.

Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp) is one of the drug efflux transporters that triggers multidrug resistance (MDR) in cells. Herein, by utilizing the strategies of active skeleton splicing and structural optimization on the lead compound 5 m, a total of 50 novel 2,5-disubstituted furan derivatives were designed, synthesized, and screened for P-gp inhibitory activity. The structure-activity relationship analysis enabled the identification of an important pharmacophore N-phenylbenzamide, which resulted in the discovery of a promising drug lead compound Ⅲ-8.

Novel pyrimidin-4-one derivatives as potential T3SS inhibitors against Xanthomonas campestris pv. campestris.

Background: Cruciferous black rot is caused by Xanthomonas campestris pv. campestris (Xcc) infection and is a widespread disease worldwide. Excessive and repeated use of bactericide is an important cause of the development of bacterial resistance.

Synthesis and biological evaluation of 2,5-disubstituted furan derivatives containing 1,3-thiazole moiety as potential α-glucosidase inhibitors.

α-Glucosidase, which is involved in the hydrolysis of carbohydrates to glucose and directly mediates blood glucose elevation, is a crucial therapeutic target for type 2 diabetes. In this work, 2,5-disubstituted furan derivatives containing 1,3-thiazole-2-amino or 1,3-thiazole-2-thiol moiety (III-01 ∼ III-30) were synthesized and screened for their inhibitory activity against α-glucosidase. α-Glucosidase inhibition assay demonstrated that all compounds had IC in the range of 0.

2,5-Disubstituted furan derivatives containing imidazole, triazole or tetrazole moiety as potent α-glucosidase inhibitors.

α-Glucosidase inhibitors (AGIs) are oral antidiabetic drugs, preferably used in treating type 2 diabetes mellitus, that delay the absorption of carbohydrates from the gastrointestinal system. In this work, 2,5-disubstituted furan derivatives containing imidazole, triazole or tetrazole moiety (III-01 ∼ III-45) were synthesized and characterized by elemental analysis, HRMS, H NMR, C NMR and single crystal X-ray. Their inhibitory activity against α-glucosidase was screened.

Diversity-oriented synthesis of fluoroalkylated amines the palladium-catalyzed divergent fluoroalkylamination of 1,3-dienes.

Herein, we reported the first versatile and expeditious protocol for the diversity-oriented synthesis (DOS) of fluoroalkylated amines the photoinduced palladium-catalyzed cross coupling of 1,3-dienes, amines and fluoroalkyl iodides, which features excellent 3,4- and 1,4-selectivity controlled by fluoroalkyl iodides, a broad substrate scope as well as good function group tolerance, and could be extended to the late-stage modification of bioactive molecules.

Discovery of a series of 5-phenyl-2-furan derivatives containing 1,3-thiazole moiety as potent Escherichia coli β-glucuronidase inhibitors.

Gut microbial β-glucuronidases have drawn much attention due to their role as a potential therapeutic target to alleviate some drugs or their metabolites-induced gastrointestinal toxicity. In this study, fifteen 5-phenyl-2-furan derivatives containing 1,3-thiazole moiety (1-15) were synthesized and evaluated for their inhibitory effects against Escherichia coli β-glucuronidase (EcGUS). Twelve of them showed satisfactory inhibition against EcGUS with IC values ranging from 0.

Merging C(sp)-H activation with DNA-encoding.

DNA-encoded library (DEL) technology has the potential to dramatically expedite hit identification in drug discovery owing to its ability to perform protein affinity selection with millions or billions of molecules in a few experiments. To expand the molecular diversity of DEL, it is critical to develop different types of DNA-encoded transformations that produce billions of molecules with distinct molecular scaffolds. Sequential functionalization of multiple C-H bonds provides a unique avenue for creating diversity and complexity from simple starting materials.

Design, synthesis and bioactivity study on 5-phenylfuran derivatives as potent reversal agents against P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a phenomenon in which cells become resistant to structurally and mechanistically unrelated drugs resulting in low intracellular drug concentrations. It is one of the noteworthy problems in malignant tumor clinical therapeutics. So P-gp protein is one of the ideal targets to solve MDR.

2,5-Disubstituted furan derivatives containing 1,3,4-thiadiazole moiety as potent α-glucosidase and E. coli β-glucuronidase inhibitors.

In this paper, the 2,5-disubstituted furan derivatives containing 1,3,4-thiadiazole were synthesized and screened for their inhibitory activity against α-glucosidase and β-glucuronidases to obtain potent α-glucosidase inhibitor 9 (IC = 0.186 μM) and E. coli β-glucuronidase inhibitor 26 (IC = 0.

Synthesis and bioactivity of phenyl substituted furan and oxazole carboxylic acid derivatives as potential PDE4 inhibitors.

In this present study, a series of 5-phenyl-2-furan and 4-phenyl-2-oxazole derivatives were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. In vitro results showed that the synthesized compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNF-α release. Among the designed compounds, Compound 5j exhibited lower IC value (1.

Thiazolidin-2-cyanamides derivatives as novel potent β-glucuronidase inhibitors and their structure-inhibitory activity relationships.

Gut microbial β-glucuronidases have the ability to deconjugate glucuronides of some drugs, thus have been considered as an important drug target to alleviate the drug metabolites-induced gastrointestinal toxicity. In this study, thiazolidin-2-cyanamide derivatives containing 5-phenyl-2-furan moiety () were evaluated for inhibitory activity against β-glucuronidase (EcGUS). All of them showed more potent inhibition than a commonly used positive control, d-saccharic acid 1,4-lactone, with the IC values ranging from 1.

Discovery of novel inhibitors of phosphodiesterase 4 with 1-phenyl-3,4-dihydroisoquinoline scaffold: Structure-based drug design and fragment identification.

Currently, it is in urgent need to develop novel selective PDE4 inhibitors with novel structural scaffolds to overcome the adverse effects and improve the efficacy. Novel 1-phenyl-3,4-dihydroisoquinoline amide derivatives were developed as potential PDE4 inhibitors based on the structure-based drug design and fragment identification strategy. A SARs analysis was performed in substituents attached in the C-3 side chain phenyl ring, indicating that the attachment of methoxy group or halogen atom substitution at the ortho-position of the phenyl ring was helpful to enhance both inhibitory activity toward PDE4B and selectivity.

Novel -Thiazol-2-yl-furan-2-carbothioate Derivatives as Potential T3SS Inhibitors Against on Rice.

Bacterial leaf blight (BLB) caused by pv () is considered as the most destructive disease of rice. The use of bactericides is among the most widely used traditional methods to control this destructive disease. The excessive and repeated use of the same bactericides is also becoming the reason behind the development of bactericide resistance.