Design, synthesis, and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols.
Based on the results of computational docking to the active site of the cytochrome P450 14alpha-demethylase (CYP51), a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols as analogs of fluconazole were designed, synthesized, and evaluated as antifungal agents. Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent activities with broad spectrum.
Chai
Xiaoyun
X
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Guohe Road 325, Shanghai 200433, People's Republic of China.
Zhang
Jun
J
Yu
Shichong
S
Hu
Honggang
H
Zou
Yan
Y
Zhao
Qingjie
Q
Dan
Zhigang
Z
Zhang
Dazhi
D
Wu
Qiuye
Q
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D015195:Drug Design; D015725:Fluconazole / Q000138:chemical synthesis* / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D020005:Propanols / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D014230:Triazoles / Q000737:chemistry
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D005656:Fungal Proteins; D020005:Propanols; D014230:Triazoles; C465525:cytochrome P-450 CYP51, Candida albicans; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System