Design,synthesis and evaluation of the compounds combined with fluconazole against drug resistant Candida albicans
10.3969/j.issn.1006-0111.2016.02.009
- VernacularTitle:协同氟康唑抗耐药白念珠菌化合物的设计合成及活性研究
- Author:
Jing ZHAO
1
;
Ran LI
;
Li DAI
;
Zhan CAI
;
Dazhi ZHANG
;
Yuanying JIANG
Author Information
1. 福建中医药大学药学院
- Keywords:
antifungal;
drug resistant;
synergism;
synthesis;
Candida albicans
- From:
Journal of Pharmaceutical Practice
2016;34(2):129-134
- CountryChina
- Language:Chinese
-
Abstract:
Objective 3,4-Methylenedioxyphenethylamine and caffeic acid derivatives have been proven previously in our group to produce activity against drug resistant fungi synergistic with fluconazole (FCZ).The two pharmacophores were cou-pled by amino acids as linkers in this project in order to design and synthesize the novel compounds and investigate the activity against drug resistant fungi in vitro.Methods 3,4-Methylenedioxyphenethylamine initially reacted with Boc-protected amino acids,following deprotection and coupling reaction with caffeic acid,to get nine title compounds.All title compounds as well as four intermediates were subjected to antifungal activity screening for fluconazole resistant Candida albicans in vitro.Results Nine title compounds showed synergistic antifungal activity for drug resistant Candida albicans with fluconazole at a concentra-tion range of 0.5-2.0μg/ml.Among them,compounds 3b,3f,3g and 3i showed the higher activity with the same MIC80 value of 0.5 μg/ml,which is comparable to those of the control compounds 7b and 5.Conclusion Linking 3,4-methylenedioxyphen-ethylamine and caffeic acid with piperidine-4-carboxylic acid (3b),valine (3g),leucine (3f) and isoleucine (3i) led to novel compounds with high synergistic antifungal activity against drug resistant Candida albicans combined with fluconazole.
