香豆素苯并三唑的合成、抗微生物活性及其与氯霉素和氟康唑协同作用研究

以间苯二酚为起始原料,经过环化、醚化、N-烷化等多步反应合成了一系列新型香豆素苯并三唑类化合物,其结构经1H NMR、IR、MS和元素分析证实。体外考察了合成的香豆素类化合物抗革兰阳性菌、革兰阴性菌及真菌活性。结果表明香豆素苯并三唑能有效抑制细菌和真菌的生长,其中化合物11a～11e和13a～13c抗普通变形杆菌ATCC 6896活性强于氯霉素(chloromycin)。化合物11a和11b抑制金葡菌ATCC 25923和藤黄微球菌ATCC 4698的生长能力与氯霉素相当。化合物11a～11d抗烟曲霉菌ATCC 96918活性优于氟康唑(fluconazole)。此外,氯霉素或氟康唑与香豆素苯并三唑联用后,不仅减少了用药剂量,还拓宽了抗微生物谱,尤其增强了抑制耐甲氧西林的金葡菌N 315和氟康唑不敏感的烟曲霉菌的生长能力。

Synthesis and antimicrobial evaluation of coumarin-based benzotriazoles and their synergistic effects with chloromycin and fluconazole

A series of new coumarin-based benzotriazole derivatives were successfully synthesized via a multi-step sequence of cyclization,etherification and N-alkylation,and were confirmed by 1H NMR,IR,MS spectra as well as elemental analyses.All these synthesized coumarin compounds were evaluated for in vitro antimicrobial activities against four Gram-positive bacteria,four Gram-negative bacteria and three fungi by two fold serial dilution technique.The bioactive assay showed that all these prepared coumarin benzotr...