Green efficient synthesis of urease and acetylcholinesterase inhibiting anisaldehyde derivatives and their in-silico studies

Abstract

New synthetic organic compounds are needed in the medical, industrial, and agricultural fields. Urease inhibitors are usually added to urea formulations used to prevent hydrolysis of urea to ammonia. Acetylcholinesterase inhibitors are used to treat neurodegenerative disorders. In the present work, mechanochemical green and conventional reflux methods were compared to synthesize anisaldehyde derivatives, 2,4-dichloro-N-(4-methoxybenzylidene)aniline (SB1) and 3,4-dichloro-N-(4-methoxybenzylidene)aniline (SB2), which were reduced to their corresponding amines, RSB1 and RSB2. The structures of the compounds were determined based on spectroscopic studies. The compounds showed good urease and acetylcholinesterase inhibitory activity. The SB1 (IC50 0.027 µM) showed good urease inhibitory activity as compared to the positive control thiourea (IC50 0.065 µM). SB2 (IC50 0.091 µM), had notable acetylcholinesterase inhibitory activity as compared to the standard Neostigmine (IC50 0.008 µM). The SB1 and SB2 showed weak radical scavenging activity in DPPH and ABTS assays than RSB1 and RSB2. They were more active in ABTS assay than DPPH. In ABTS assay RSB2 and RSB1 showed good antioxidant activity (EC50 0.03 µM, 0.04 µM) as compared to SB1 and SB2 (EC50 0.07 µM, EC50 0.06 µM) as compared by standard ascorbic acid (EC50 0.05 µM). SB2 showed higher total antioxidant capacity than other compounds. Molecular docking studies showed the considerable binding potential of SB1, SB2, RSB1, and RSB2 with acetylcholinesterase and urease which was further confirmed by calculating the binding free energy through MMGBSA (Molecular Mechanics/Generalized Born Surface Area). Binding free energies conceded good consistency with inhibitory profiles of acetylcholinesterase and urease.