Medicinal Chemistry Research

, Volume 28, Issue 4, pp 571–579 | Cite as

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

  • 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-YañezEmail author
Original Research


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.


1,2,3-Triazoles Antifungal Click chemistry Fluconazole analogues 



This work was supported by COMECYT (fellowship for AZH) and ASCILA (fellowship for DDCC). Financial support from CONACYT is also gratefully acknowledged. The authors would like to thank Signa S.A. de C. V. for some kindly donated solvents and reagents and to N. Zavala, A. Nuñez, and L. Triana for the technical support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2317_MOESM1_ESM.pdf (7.1 mb)
Supplementary Data


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Armando Zambrano-Huerta
    • 1
    • 3
  • Damián David Cifuentes-Castañeda
    • 1
  • Joanatan Bautista-Renedo
    • 1
  • Hugo Mendieta-Zerón
    • 2
  • Roberto Carlos Melgar-Fernández
    • 3
  • Sergio Pavón-Romero
    • 4
  • Macario Morales-Rodríguez
    • 4
  • Bernardo A. Frontana-Uribe
    • 1
  • Nelly González-Rivas
    • 1
  • Erick Cuevas-Yañez
    • 1
    Email author
  1. 1.Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM. Universidad Autónoma del Estado de MéxicoTolucaMexico
  2. 2.Facultad de MedicinaUniversidad Autónoma del Estado de MexicoTolucaMexico
  3. 3.Signa S.A. de C.V., Av. Industria Automotriz No. 301, Zona Industrial TolucaTolucaMexico
  4. 4.Departamento de Microbiología, Facultad de QuímicaUniversidad Autónoma del Estado de MexicoTolucaMexico

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