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
- Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM. Universidad Autónoma del Estado de México (Mexico)
- Universidad Autónoma del Estado de Mexico, Facultad de Medicina (Mexico)
- Signa S.A. de C.V., Av. Industria Automotriz No. 301, Zona Industrial Toluca (Mexico)
- Universidad Autónoma del Estado de Mexico, Departamento de Microbiología, Facultad de Química (Mexico)
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 (R{sup 1} = F and R{sup 2} = 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.
- OSTI ID:
- 22936201
- Journal Information:
- Medicinal Chemistry Research (Print), Journal Name: Medicinal Chemistry Research (Print) Journal Issue: 4 Vol. 28; ISSN 1054-2523
- Country of Publication:
- United States
- Language:
- English
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