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. 2021 Sep 13;6(38):24879-24890.
doi: 10.1021/acsomega.1c03734. eCollection 2021 Sep 28.

New 1,2,3-Triazole-Appended Bis-pyrazoles: Synthesis, Bioevaluation, and Molecular Docking

Ashruba B Danne  1 , Mukund V Deshpande  2 , Jaiprakash N Sangshetti  3 , Vijay M Khedkar  4 , Bapurao B Shingate  1
Affiliations

New 1,2,3-Triazole-Appended Bis-pyrazoles: Synthesis, Bioevaluation, and Molecular Docking

Ashruba B Danne et al. ACS Omega. .

Abstract

The present work describes design of a small library of new 1,2,3-triazole-appended bis-pyrazoles by using a molecular hybridization approach, and the synthesized hybrids were evaluated for their antifungal activity against different fungal strains, namely, Candida albicans, Cryptococcus neoformans, Candida glabrata, Candida tropicalis, Aspergillus niger, and Aspergillus fumigatus. All the compounds exhibited broad-spectrum activity against the tested fungal strains with excellent minimum inhibitory concentration values. The molecular docking study against sterol 14α-demethylase (CYP51) could provide valuable insights into the binding modes and affinity of these compounds. Furthermore, these compounds were also evaluated for their antioxidant activity, which also resulted in promising data.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Structures of the bioactive bis-pyrazole-based molecules.
Figure 2
Figure 2
Structures of 1,2,3-triazole-containing drugs.
Figure 3
Figure 3
Molecular design strategy of triazole-appended bis-pyrazole derivatives.
Scheme 1
Scheme 1. Synthesis of 1,2,3-Triazole-Appended Bis-pyrazole Derivatives
Figure 4
Figure 4
Structures of the synthesized 1,2,3-triazole-appended bis-pyrazole derivatives.
Figure 5
Figure 5
Binding mode of 13e into the active site of sterol 14α-demethylase (CYP51) (on right side: green lines signify π–π stacking interactions, while the pink lines represent the hydrogen bonding interactions).
Figure 6
Figure 6
Binding mode of 13a, 13b, 13c, 13d, 13f, 13g, 13h, and 13i into the active site of sterol 14α-demethylase (CYP51) (on right side: green lines signify π–π stacking interactions, while the pink lines represent the hydrogen bonding interactions).
Figure 6
Figure 6
Binding mode of 13a, 13b, 13c, 13d, 13f, 13g, 13h, and 13i into the active site of sterol 14α-demethylase (CYP51) (on right side: green lines signify π–π stacking interactions, while the pink lines represent the hydrogen bonding interactions).
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