新型氮唑类化合物的合成及抗真菌活性研究

Synthesis and antifungal activity of the novel azole compounds

目的设计合成含有1,3,4-二唑侧链的新型氮唑类化合物,并研究其体外抗真菌活性。方法通过酰化、胺解、环合、亲核取代等多步反应合成了14个未见文献报道的目标化合物,其结构通过1 H NMR、MS确证,选择6种真菌为实验菌株,用微量液体稀释法检测目标化合物的体外抑菌活性。结果所有目标化合物对实验菌株均有一定的抑制活性,尤其对白念珠菌活性较好。化合物10d、10i、10l、10n对白念珠菌的MIC_(80)值为0.003 9μg/ml,是伊曲康唑(MIC_(80):0.062 5μg/ml)的16倍,是氟康唑(MIC_(80):0.25μg/ml)的64倍。结论 1,3,4-二唑侧链结构的引入对化合物的活性有影响,可能是侧链结构中二唑环与苯环能够与靶酶较好地结合,从而提高了化合物的活性。

Objective To design and synthesize novel triazole antifungal derivatives with 1,3,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation, aminolysis reaction, cyelization, nucleophilic substitution, etc. All the compounds were characterized by 1 H NMR, MS spectra. The in vitro antifungal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi, especially against Candida albicans. Compounds 10d, 10i, 101, and 10n were found to be the most effective, with a minimum inhibitory concentration （MICro） of 0. 003 9 μg/ml. They are 16-fold more potent than ICZ （ MIC80 0. 062 5 μg/ml） and 64-fold more potent than FCZ （MIC80 0.25 μg/ml）. Conclusion The 1,3,4-oxadiazole side chain could affect the antifungal activities. That could be due to the proper incorporation between the 1,3,4-oxadiazole substituted phenyl ring with the target enzyme.