Click-chemistry-inspired synthesis of new series of 1,2,3-triazole fused chromene with glucose triazole conjugates: Antibacterial activity assessment with molecular docking evaluation

• Published in: Carbohydrate research Vol. 543; p. 109222
• Main Authors: Ahemad, Mohammed Ansar, Patra, Arpita, Muduli, Lipsarani, Nayak, Sabita, Mohapatra, Seetaram, Panda, Jasmine, Sahoo, Chita Ranjan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-09-2024
• Subjects: 1,2,3-Triazole fused chromene; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Click Chemistry; CuAAC; DNA Gyrase - chemistry; DNA Gyrase - metabolism; Escherichia coli - drug effects; Glucose - analogs & derivatives; Glucose - chemistry; Glucose triazole; Humans; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Molecular Structure; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; Antibacterial activity; Glucose triazole; 1,2,3-Triazole fused chromene; Molecular docking; CuAAC
• ISSN: 0008-6215; 1873-426X; 1873-426X
• DOI: 10.1016/j.carres.2024.109222

A series of new 1,2,3-triazole fused chromene based glucose triazole conjugates were synthesized from chromene fused 1,2,3-triazolyl extended alkyne and 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl azide in good to excellent yield by a copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The major advantages include mild reaction conditions, high yield, good substrate scope, and shorter reaction time. The antibacterial efficacy of the compounds were assessed in vitro against human pathogenic Gram-negative E. coli and Gram-positive S. aureus bacteria. Compound 24j was found to be the most potent molecule with zone of inhibition (ZI) of 17 mm and minimum inhibitory concentration (MIC) of 25 μg mL−1 in E. coli and ZI of 16 mm and MIC of 25 μg mL−1 in S. aureus. Also, it significantly inhibited E. coli DNA-gyrase in silico with a binding affinity of −9.4 kcal/mol. Among all the synthesized compounds, 24i, 24d, 24e and 24f showed significant antibacterial activity against both strains and inhibited DNA-gyrase in silico with good binding affinities. Hence, these 1,2,3-triazole fused chromene based glucose triazole conjugates may evolve to be powerful antibacterial agents in recent future, according to structure-activity relationships based on strong antibacterial properties and molecular docking studies.
[Display omitted]
•Novel 1,2,3-triazole fused chromene based glucose triazole conjugates were synthesized by a copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction.•Major advantages of this protocol include mild reaction conditions, high yield, good substrate scope and shorter reaction time.•The antibacterial efficacy of the compounds were assessed in vitro against Gram-negative E. coli and Gram-positive S. aureus bacteria by the agar-well diffusion method.•Molecular docking studies were studied with E. coli DNA-gyrase.•Almost all compounds showed significant antibacterial activity against both strains and inhibited DNA-gyrase in silico with good binding affinities.