以亚色烯稠合的1,2,3-三唑基延伸的炔烃和2,3,4,6-四-O-乙酰基-β-d-吡喃葡萄糖基叠氮化物为原料,通过铜催化的叠氮化物-炔环加成(CuAAC)反应,合成了一系列新的1,2,3-三唑稠合的基于亚甲基的葡萄糖三唑缀合物。主要优点包括温和的反应条件,高产,良好的基材范围,更短的反应时间。在体外评估化合物对人致病性革兰氏阴性大肠杆菌和革兰氏阳性金黄色葡萄球菌的抗菌功效。发现化合物24j是最有效的分子,在大肠杆菌中具有17mm的抑制区(ZI)和25μgmL-1的最小抑制浓度(MIC),在金黄色葡萄球菌中具有16mm的ZI和25μgmL-1的MIC。此外,它以-9.4kcal/mol的结合亲和力显着抑制计算机中的大肠杆菌DNA促旋酶。在所有合成的化合物中,24i,24d,24e和24f对两种菌株均显示出显着的抗菌活性,并以良好的结合亲和力抑制了DNA-促旋酶。因此,这些1,2,3-三唑稠合色烯基葡萄糖三唑偶联物可能在最近的未来发展成为强大的抗菌剂,根据基于强抗菌性能和分子对接研究的构效关系。
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.