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Title: 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

Abstract

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.

Authors:
; ;  [1];  [2];  [3]; ;  [4]; ; ;  [1]
  1. Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM. Universidad Autónoma del Estado de México (Mexico)
  2. Universidad Autónoma del Estado de Mexico, Facultad de Medicina (Mexico)
  3. Signa S.A. de C.V., Av. Industria Automotriz No. 301, Zona Industrial Toluca (Mexico)
  4. Universidad Autónoma del Estado de Mexico, Departamento de Microbiología, Facultad de Química (Mexico)
Publication Date:
OSTI Identifier:
22936201
Resource Type:
Journal Article
Journal Name:
Medicinal Chemistry Research (Print)
Additional Journal Information:
Journal Volume: 28; Journal Issue: 4; Other Information: Copyright (c) 2019 Springer Science+Business Media, LLC, part of Springer Nature; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 1054-2523
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKYNES; ARTEMIA; AZIDES; CANDIDA; COPPER; HALOGENS; TOXICITY; TRIAZOLES

Citation Formats

Zambrano-Huerta, Armando, Cifuentes-Castañeda, Damián David, Bautista-Renedo, Joanatan, Mendieta-Zerón, Hugo, Melgar-Fernández, Roberto Carlos, Pavón-Romero, Sergio, Morales-Rodríguez, Macario, Frontana-Uribe, Bernardo A., González-Rivas, Nelly, and Cuevas-Yañez, Erick. 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. United States: N. p., 2019. Web. doi:10.1007/S00044-019-02317-5.
Zambrano-Huerta, Armando, Cifuentes-Castañeda, Damián David, Bautista-Renedo, Joanatan, Mendieta-Zerón, Hugo, Melgar-Fernández, Roberto Carlos, Pavón-Romero, Sergio, Morales-Rodríguez, Macario, Frontana-Uribe, Bernardo A., González-Rivas, Nelly, & Cuevas-Yañez, Erick. 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. United States. https://doi.org/10.1007/S00044-019-02317-5
Zambrano-Huerta, Armando, Cifuentes-Castañeda, Damián David, Bautista-Renedo, Joanatan, Mendieta-Zerón, Hugo, Melgar-Fernández, Roberto Carlos, Pavón-Romero, Sergio, Morales-Rodríguez, Macario, Frontana-Uribe, Bernardo A., González-Rivas, Nelly, and Cuevas-Yañez, Erick. 2019. "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". United States. https://doi.org/10.1007/S00044-019-02317-5.
@article{osti_22936201,
title = {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},
author = {Zambrano-Huerta, Armando and Cifuentes-Castañeda, Damián David and Bautista-Renedo, Joanatan and Mendieta-Zerón, Hugo and Melgar-Fernández, Roberto Carlos and Pavón-Romero, Sergio and Morales-Rodríguez, Macario and Frontana-Uribe, Bernardo A. and González-Rivas, Nelly and Cuevas-Yañez, Erick},
abstractNote = {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.},
doi = {10.1007/S00044-019-02317-5},
url = {https://www.osti.gov/biblio/22936201}, journal = {Medicinal Chemistry Research (Print)},
issn = {1054-2523},
number = 4,
volume = 28,
place = {United States},
year = {2019},
month = {4}
}