Synthesis of 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles, Antifungal Activity and In Silico Analysis

Author(s): Luciana Terra, Daiane de Jesus Viegas, Alice Maria Rolim Bernardino, Jéssica Venância Faria, Percilene Fazolin Vegi, Rômulo Gabriel De Miranda de Paula Pinto, Maurício Silva dos Santos, Helena Carla Castro, Paula Alvarez Abreu*

Journal Name: Letters in Organic Chemistry

Volume 17 , Issue 10 , 2020

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Graphical Abstract:


Serious fungal infections are increasing worldwide and have become a great concern in the medical field since antifungal drugs are restricted to a few drug classes. This work aims to evaluate the antifungal activity of a series of 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (1a-g) and to establish a structure-activity relationship (SAR). The synthesis of these compounds was carried out in a single step followed by cyclization in good to excellent yields i.e. 73-94%. The chemical structures were confirmed by melting point, IR, 1H-NMR, 13C-NMR, and HRMS. These seven compounds were submitted to the disk diffusion test against Candida spp. and the active compound was evaluated by means of the microdilution method to determine the minimum inhibitory concentration (MIC). In addition, the stereo electronic descriptors were evaluated and pharmacokinetic and toxicological properties were calculated to predict the potential of these compounds as a drug. All the compounds presented good theoretical physicochemical parameters and one of them showed reasonably good antifungal activity.

Keywords: Pyrazoles, antifungal agents, structure-activity relationship, drug discovery, pharmacokinetic, toxicity tests, molecular modeling.

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Article Details

Year: 2020
Published on: 17 November, 2020
Page: [779 - 787]
Pages: 9
DOI: 10.2174/1570178617666200210105246
Price: $65

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