Design, synthesis, theoretical study, antioxidant, and anticholinesterase activities of new pyrazolo-fused phenanthrolines

Abstract

Pyrazole-fused phenanthroline compounds were obtained through several synthetic routes. NMR, HRMS, and IR techniques were used to characterize and confirm the chemical structures. Crystal structures were obtained from compounds 3a, 5b, 5j, 5k, and 5n and analyzed using X-ray diffraction. Compounds were evaluated as acetyl (AChE) and butyrylcholinesterase (BChE) inhibitors, and the results showed a moderate activity. Compound 5c presented the best activity against AChE (IC₅₀ = 53.29 μM) and compound 5l against BChE enzyme (IC₅₀ = 119.3 μM). Furthermore, the ability of the synthetic compounds to scavenge cationic radicals DPPH and ABTS was evaluated. Compound 5e (EC₅₀ = 26.71 μg mL⁻¹) presented the best results in the DPPH assay, and compounds 5e, 5f and 5g (EC₅₀ = 11.51, 3.10 and <3 μg mL⁻¹, respectively) showed better ABTS cationic radical scavenging results. Finally, in silico analyses indicated that 71% of the compounds show good oral availability and are within the ranges established by the Lipinski criteria.