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

Autor: Macario Morales-Rodríguez, Sergio H. Pavón-Romero, Damián David Cifuentes-Castañeda, Joanatan M. Bautista-Renedo, Hugo Mendieta-Zerón, Roberto Carlos Melgar-Fernández, Armando Zambrano-Huerta, Erick Cuevas-Yañez, Nelly González-Rivas, Bernardo A. Frontana-Uribe
Rok vydání: 2019
Předmět:
Zdroj: Medicinal Chemistry Research. 28:571-579
ISSN: 1554-8120
1054-2523
DOI: 10.1007/s00044-019-02317-5
Popis: 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.
Databáze: OpenAIRE
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