Abstract
A new series of 1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles 4a-f, were prepared via a Knoevenagel condensation reaction followed by Michael addition for their antimicrobial and antioxidant properties, through the one-pot three-component reaction of 3-indolyl-3-oxopropanenitrile (1), aromatic aldehydes 2 and 1H-pyrazol-5-amines 3 in ethanol in the presence of triethylamine as a catalyst, which upon cyclization and auto-oxidation yielded the corresponding product in excellent proportion. Elemental analysis and spectroscopic methods were used to investigate the novel derivatives. The newly synthesized compounds' antibacterial and antioxidant properties were assessed, and their interactions with important proteins were investigated using molecular docking. Strong action was demonstrated by compounds 4a, 4c, and 4f against the bacterial strains P. aeruginosa, K. pneumoniae, S. aureus, and E. coli. DPPH radical scavenging techniques were used to evaluate their antioxidant capacities, demonstrating their capacity to counteract oxidative stress. Molecular docking and ADMET/drug-likeness screening revealed favorable binding energies and adherence to Lipinski's rules, indicating these compounds could be promising orally bioavailable drug candidates.