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Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones.
Biochem Biophys Res Commun. 2017 Jan 22; 482(4):615-624.BB

Abstract

Super-activation of cholinesterases (acetylcholinesterase and butyrylcholinesterase) are linked to various neurological problems most precisely Alzheimer's disease (AD), which leads to senile dementia. Therefore, cholinesterases (AChE & BChE) inhibition are considered as a promising strategy for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of AD, belong to a group of cholinesterase inhibitors. However, none of them is able to combat or completely abrogate the disease progression. Herein, we report a series of newly synthesized chalcone derivatives with anti-AD potential. For this purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones were tested for their cholinesterases (AChE & BChE) inhibitory activity. All compounds were found as selective inhibitor of AChE. In piperidyl chalcones derivatives compound 1e having IC50 of 0.16 ± 0.008 μM and 2m in 2-pyrazoline chalcones with IC50 of 0.13 ± 0.006 μM, were found to be the most potent inhibitors of AChE, exhibiting ≈142 and ≈ 173-fold greater inhibitory potential compared to the reference inhibitor i.e., Neostigmine (IC50 ± SEM = 22.2 ± 3.2 μM). Molecular docking studies of most potent inhibitors were carried out to investigate the binding interactions inside the active site. Molecular docking study revealed that potent compounds and co-crystalized ligand had same binding orientation within the active site of target enzyme. Most of these compounds are selective inhibitors of AChE with a potential use against progressive neurodegenerative disorder and age related problems.

Authors+Show Affiliations

Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Abbottabad, Pakistan; Division of Analytical Chemistry, Institute of Chemical Science, Bahauddin Zakariya University, 60800, Multan, Pakistan.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Abbottabad, Pakistan.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Abbottabad, Pakistan.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Abbottabad, Pakistan.Institute of Chemistry, University of the Punjab, Lahore, Pakistan.Division of Analytical Chemistry, Institute of Chemical Science, Bahauddin Zakariya University, 60800, Multan, Pakistan.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Abbottabad, Pakistan. Electronic address: drjamshed@ciit.net.pk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27865835

Citation

Shah, Muhammad Shakil, et al. "Cholinesterases Inhibition and Molecular Modeling Studies of Piperidyl-thienyl and 2-pyrazoline Derivatives of Chalcones." Biochemical and Biophysical Research Communications, vol. 482, no. 4, 2017, pp. 615-624.
Shah MS, Khan SU, Ejaz SA, et al. Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones. Biochem Biophys Res Commun. 2017;482(4):615-624.
Shah, M. S., Khan, S. U., Ejaz, S. A., Afridi, S., Rizvi, S. U. F., Najam-Ul-Haq, M., & Iqbal, J. (2017). Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones. Biochemical and Biophysical Research Communications, 482(4), 615-624. https://doi.org/10.1016/j.bbrc.2016.11.082
Shah MS, et al. Cholinesterases Inhibition and Molecular Modeling Studies of Piperidyl-thienyl and 2-pyrazoline Derivatives of Chalcones. Biochem Biophys Res Commun. 2017 Jan 22;482(4):615-624. PubMed PMID: 27865835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones. AU - Shah,Muhammad Shakil, AU - Khan,Shafi Ullah, AU - Ejaz,Syeda Abida, AU - Afridi,Saifullah, AU - Rizvi,Syed Umar Farooq, AU - Najam-Ul-Haq,Muhammad, AU - Iqbal,Jamshed, Y1 - 2016/11/16/ PY - 2016/11/09/received PY - 2016/11/14/accepted PY - 2016/11/21/pubmed PY - 2017/5/30/medline PY - 2016/11/21/entrez KW - 2-Pyrazoline derivatives of chalcones KW - Alzheimer's disease KW - Cholinesterases inhibitors KW - Molecular docking KW - Piperidyl-thienyl derivatives SP - 615 EP - 624 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 482 IS - 4 N2 - Super-activation of cholinesterases (acetylcholinesterase and butyrylcholinesterase) are linked to various neurological problems most precisely Alzheimer's disease (AD), which leads to senile dementia. Therefore, cholinesterases (AChE & BChE) inhibition are considered as a promising strategy for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of AD, belong to a group of cholinesterase inhibitors. However, none of them is able to combat or completely abrogate the disease progression. Herein, we report a series of newly synthesized chalcone derivatives with anti-AD potential. For this purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones were tested for their cholinesterases (AChE & BChE) inhibitory activity. All compounds were found as selective inhibitor of AChE. In piperidyl chalcones derivatives compound 1e having IC50 of 0.16 ± 0.008 μM and 2m in 2-pyrazoline chalcones with IC50 of 0.13 ± 0.006 μM, were found to be the most potent inhibitors of AChE, exhibiting ≈142 and ≈ 173-fold greater inhibitory potential compared to the reference inhibitor i.e., Neostigmine (IC50 ± SEM = 22.2 ± 3.2 μM). Molecular docking studies of most potent inhibitors were carried out to investigate the binding interactions inside the active site. Molecular docking study revealed that potent compounds and co-crystalized ligand had same binding orientation within the active site of target enzyme. Most of these compounds are selective inhibitors of AChE with a potential use against progressive neurodegenerative disorder and age related problems. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/27865835/Cholinesterases_inhibition_and_molecular_modeling_studies_of_piperidyl_thienyl_and_2_pyrazoline_derivatives_of_chalcones_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(16)31945-3 DB - PRIME DP - Unbound Medicine ER -