Synthesis, Characterization, Antimicrobial Activity and Molecular Docking Studies of Novel Pyrano[2,3-c]Pyrazole Derivatives

Abstract

Antimicrobial activity is one of the most critical functional properties of β-enaminonitriles, pyranopyrazoles, and pyrazolopyranopyrimidines since bacteria and fungi very quickly attack these heterocycles. Therefore, a series of novel β-enaminonitriles (3a–d) were constructed by different pathways. An efficient MCR of these derivatives involving β-ketoesters, 2,4-dinitrophenylhydrazine, malononitrile, and aromatic aldehydes using different catalysts under reaction conditions with excellent yields is established. The β-enaminonitrile (3a) was used as a key intermediate for the synthesis of heterocycles as pyrazolopyranopyrimidines (4, 6) and pyranopyrazoles (5, 7, and 8). The chemical structures were confirmed through elemental analysis and spectral data as FT-IR,¹H-NMR,¹³C-NMR, and mass spectra. The antibacterial activity of the synthesized compounds has been tested against Gram-positive bacteria (Bacillus cereus, Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa). The compounds (3a, 3b, and 3d) showed good antibacterial activity, but compound (3c) displayed a potent high inhibitory activity Additionally, the antifungal activity has been tested against Aspergillus niger, Penicillium sp. and Candida albicans, the compound (3a, 3b, 3d, 4, and 6) showed good antifungal activity. The potential inclusion of nitro substituents may undoubtedly increase the activity of these compounds. Based on the inhibition zone determination, the results indicated that these novel heterocycles improve their antimicrobial activity. The molecular docking was studied, Tyrosyl-tRNA synthetase binding affinities and viable interaction modes were rationalized using a molecular docking study conducted against S. aureus bacteria.