Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies |
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| Affiliation: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia;2. Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;3. Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;4. Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia;5. Department of Pharmacology, Faculty of Medicine, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia;6. Department of Pharmaceutics, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia;1. Department of Physics, St John’s University, United States;2. Department of Biological Sciences, St John’s University, United States;3. Department of Neurology and Neuroscience & Physiology and Psychiatry, New York University Langone Medical Center, United States;4. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, United States;5. Department of Pharmaceutical Sciences, St John''s University, United States;6. Norwegian Center for Movement Disorders, Stavanger University Hospital, 4068 Stavanger, Norway;1. Laboratory of Organic and Medicinal Chemistry, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab 151001, India;2. Department of Animal Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India;1. Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India;2. Department of Physics, Dr. MGR Educational and Research Institute University, Maduravoyal, Chennai 600095, India;3. Department of Biotechnology, Dr. MGR Educational and Research Institute University, Maduravoyal, Chennai 600095, India;4. Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India;1. Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey;2. Oltu Vocational School, Department of Food Technology, Atatürk University, 25400 Oltu, Erzurum, Turkey;3. Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia;1. Laboratory of Applied Chemistry and Environment (LCAE), Faculty of Sciences, Mohamed First University, Oujda, Morocco;2. Instituts Supérieurs des Professions Infirmières et Techniques de Santé (ISPITS), Hopital Al Farabi, Oujda, Morocco;3. CRMEF Oriental, Centre Régional des Métiers de l''Education et de Formation Oujda, Morocco |
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| Abstract: | The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68 ± 0.13 μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77 ± 0.25 μM and IC50: 12.59 ± 0.21 μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74 ± 0.09 μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52 ± 0.62 μM and IC50: 13.13 ± 0.85 μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents. |
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| Keywords: | Indole Pyrazoline Molecular docking Antioxidant Acetylcholinesterase |
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