Design, synthesis, antigiardial and in silico assessments of novel propargylamines containing nitroimidazole core

Design, synthesis, antigiardial activity, and in silico pharmacokinetic and docking assessments of new propargylamine derivatives containing 2-methyl-5-nitroimidazole core are described. These propargyl-amines were efficiently synthesized through three-component reaction (A3 coupling) between a pre-formed terminal alkyne (i.e.: 2-methyl-5-nitro-1-prop-2-ynyl-1H-imidazole), different aromatic aldehydes, and cyclic amines in refluxing toluene catalyzed by copper-doped silica cuprous sulfate (CDSCS) as a reusable, environmentally benign and low-cost nanocatalyst. The antigiardial activity of the synthesized propargilamines was in vitro investigated against Giardia lamblia (G. lamblia) and compared with metronidazole (MTZ) as a selected reference drug. Among tested compounds, 4-(1-(4-chlorophenyl)-4-(2-methyl-5-nitro-1H-imidazole-1-yl)but-2-ynyl)morpholine (2b) displayed potent antigiardial activity even stronger than MTZ. The in silico physicochemical properties, pharmacokinetic profile, and drug likeness predictions were also carried out for all synthesized compounds and MTZ. Molecular docking study was also performed to predict the binding mode and interaction of 2b with triosephosphate isomerase enzyme. This study has determined the strong binding affinity of 2b to the active site of the enzyme. (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

This study describes the design, synthesis, and evaluation of new propargylamine derivatives containing a 2-methyl-5-nitroimidazole core. The propargylamines were efficiently synthesized through a three-component reaction and their antigiardial activity was investigated. Compound 2b exhibited potent antigiardial activity. In addition, in silico analysis was performed to assess the physicochemical properties and docking interactions of the compounds.