Synthesis, In Vitro Biological Evaluation and Molecular Modeling of Benzimidazole-Based Pyrrole/Piperidine Hybrids Derivatives as Potential Anti-Alzheimer Agents

• Published in: Pharmaceuticals (Basel, Switzerland) Switzerland), 2024-04, Vol.17 (4), p.410
• Main Authors: Tariq, Sundas, Rahim, Fazal, Ullah, Hayat, Sarfraz, Maliha, Hussain, Rafaqat, Khan, Shoaib, Khan, Misbah Ullah, Rehman, Wajid, Hussain, Amjad, Bhat, Mashooq Ahmad, Farooqi, Muhammad Kamran, Shah, Syed Adnan Ali, Iqbal, Naveed
• Format: Article
• Language: English
• Subjects: AChE and BuChE and molecular docking; Alzheimer's disease; Arthritis; benzimidazole; Cancer; Drug therapy; Drugs; Enzymes; Ethanol; piperidine; pyrrole; synthesis
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17040410

Benzimidazole-based pyrrole/piperidine analogs ( - ) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds ( - ) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC = 16.11 ± 0.33 µM) and galantamine (IC = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC = 18.14 ± 0.05 µM) and galantamine (IC = 21.45 ± 0.21 µM). Similarly, synthesized compounds ( - ) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC = 20.01 ± 0.12 µM) and galantamine (IC = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC = 18.14 ± 0.05 µM) and galantamine (IC = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs , , and established numerous interactions with the active sites of targeted enzymes, with docking scores of -10.50, -9.3, -7.73 and -7.8 for AChE and -8.97, -8.2, -8.20 and -7.6 for BuChE, respectively.