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

• Published in: Journal of molecular structure 2024-11, Vol.1315, p.138845, Article 138845
• Main Authors: Khan, Shoaib, Hussain, Rafaqat, Khan, Yousaf, Iqbal, Tayyiaba, Khan, Muhammad Bilal, Al-Ahmary, Khairia Mohammed, Al Mhyawi, Saedah R.
• Format: Article
• Language: English
• Subjects: ADMET; Alzheimer's disease; Docking study; Schiff base; Sulfonamide; Triazole
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.138845

•Synthesis and spectroscopic characterization of new triazole derived Schiff base bearing sulfonamide derivatives.•Isolated compounds were evaluated for in vitro anti-Alzheimer agents.•A number of the compounds exhibited excellent activity, whereas few of them show better activity than the reference standards.•A molecular docking and ADMET studies were conducted to determine the binding interactions of the potent compounds with the enzymes active sites and their drug likeness respectively. 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 (IC50= 5.10 ± 0.20 µM, 5.70 ± 0.30 µM for AChE BuChE, respectively). These synthesized compounds displayed moderate to excellent inhibition potential with inhibitory concentration ranging between 1.90 ± 0.40 µM to 14.50 ± 0.20 µM against AChE and 2.10 ± 0.10 µM to 14.80 ± 0.40 µM against BuChE. Among the synthesized compounds, analog 4 (IC50 =1.90 ± 0.40 µM and 2.10 ± 0.10 µM) having –CF3 at para-position exhibited promising biological potency. For structural confirmation of these compounds HREI-MS and 1HNMR, 13CNMR 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. [Display omitted]