Insight into role of triazole derived Schiff base bearing sulfonamide derivatives in targeting Alzheimer ' s disease: Synthesis, characterization, in vitro and in silico assessment

Alzheimer's disease (AD), a chronic neurodegenerative disorder is reported with its high prevalence and increasing at a disturbing level across the world. Due to no availability of therapeutic drugs permanently treating AD, it became imperative to develop potent therapeutic anti-Alzheimer's agent with spellbinding efficacy and minimal side effects. With this objective, herein current study we had efficiently synthesized a novel library of triazole derived Schiff base bearing sulfonamide scaffolds ( 1 -16 ). The in vitro efficacy of these compounds as anti -Alzheimer was evaluated in contrast to Donepezil (IC 50 = 5.10 +/- 0.20 mu M, 5.70 +/- 0.30 mu M for AChE BuChE, respectively). These synthesized compounds displayed moderate to excellent inhibition potential with inhibitory concentration ranging between 1.90 +/- 0.40 mu M to 14.50 +/- 0.20 mu M against AChE and 2.10 +/- 0.10 mu M to 14.80 +/- 0.40 mu M against BuChE. Among the synthesized compounds, analog 4 (IC 50 =1.90 +/- 0.40 mu M and 2.10 +/- 0.10 mu M) having -CF 3 at para -position exhibited promising biological potency. For structural confirmation of these compounds HREI-MS and 1 HNMR, 13 CNMR techniques were employed. The binding affinity of all the lead candidates with different amino acids of targeted enzymes was studied in silico under molecular docking. Moreover, ADMET analysis was also conducted to predict the drug likeness characteristics of all the active compounds.