Synthesis and in vitro biological evaluation of 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivatives as antifungal compounds fluconazole analogues

被引：0
作者：
Armando Zambrano-Huerta
Damián David Cifuentes-Castañeda
Joanatan Bautista-Renedo
Hugo Mendieta-Zerón
Roberto Carlos Melgar-Fernández
Sergio Pavón-Romero
Macario Morales-Rodríguez
Bernardo A. Frontana-Uribe
Nelly González-Rivas
Erick Cuevas-Yañez
机构：
[1] Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM. Universidad Autónoma del Estado de México,Facultad de Medicina
[2] Universidad Autónoma del Estado de Mexico,Departamento de Microbiología, Facultad de Química
[3] Signa S.A. de C.V.,undefined
[4] Av. Industria Automotriz No. 301,undefined
[5] Zona Industrial Toluca,undefined
[6] Universidad Autónoma del Estado de Mexico,undefined
来源：
Medicinal Chemistry Research | 2019年 / 28卷
关键词：
1,2,3-Triazoles; Antifungal; Click chemistry; Fluconazole analogues;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
A novel series of 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivatives was synthesized from 1-aryl-1,3-diazidopropan-2-ol derivatives and diverse alkynes using copper catalyzed azide-alkyne cycloaddition in the key step. Most of synthesized compounds showed high activity against Candida spp. strains at a 0.04–0.5 μg/mL concentration range compared to Itraconazole and Fluconazole (MIC 2.56 and 1.28 μg/mL, respectively), which were used as reference compounds. A 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivative (R1 = F and R2 = cyclopropyl) displayed an outstanding selectivity against Candida albicans and Candida krusei (MIC = 0.0075 µg/mL). Moreover, Artemia salina bioassay on 1,3-bis-(1,2,3-triazol-1-yl)-propan-2-ol derivatives revealed low toxicity in this kind of compounds. In addition, molecular docking studies suggest good binding affinity of halogen atoms in some 1-aryl-1,3-diazidopropan-2-ol derivatives to HEME group present in 14-alpha demethylase (CYP51), which might explain the high antifungal activity found in these compounds.
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页码：571 / 579
页数：8
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