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Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies.
Bioorg Chem. 2019 10; 91:103124.BC

Abstract

To explore new scaffolds for the treat of Alzheimer's disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1H-, 13C NMR) and mass spectrometry (EI-MS). All the derivatives (1-24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes.

Authors+Show Affiliations

Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan. Electronic address: ehsan.ullah@uog.edu.pk.Department of Chemistry, Govt. College Women University, Sialkot 51300, Pakistan. Electronic address: amina.sadiq@gcwus.edu.pk.Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan.Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan.Department of Chemistry, Govt. College Women University, Sialkot 51300, Pakistan.Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan.Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan.Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.Department of Zoology, Mirpur University of Science and Technology, Mirpur 10250, Pakistan.Department of Chemistry, Govt. College Women University, Sialkot 51300, Pakistan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31319297

Citation

Mughal, Ehsan Ullah, et al. "Flavonols and 4-thioflavonols as Potential Acetylcholinesterase and Butyrylcholinesterase Inhibitors: Synthesis, Structure-activity Relationship and Molecular Docking Studies." Bioorganic Chemistry, vol. 91, 2019, p. 103124.
Mughal EU, Sadiq A, Ashraf J, et al. Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies. Bioorg Chem. 2019;91:103124.
Mughal, E. U., Sadiq, A., Ashraf, J., Zafar, M. N., Sumrra, S. H., Tariq, R., Mumtaz, A., Javid, A., Khan, B. A., Ali, A., & Javed, C. O. (2019). Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies. Bioorganic Chemistry, 91, 103124. https://doi.org/10.1016/j.bioorg.2019.103124
Mughal EU, et al. Flavonols and 4-thioflavonols as Potential Acetylcholinesterase and Butyrylcholinesterase Inhibitors: Synthesis, Structure-activity Relationship and Molecular Docking Studies. Bioorg Chem. 2019;91:103124. PubMed PMID: 31319297.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies. AU - Mughal,Ehsan Ullah, AU - Sadiq,Amina, AU - Ashraf,Jamshaid, AU - Zafar,Muhammad Naveed, AU - Sumrra,Sajjad Hussain, AU - Tariq,Rubina, AU - Mumtaz,Amara, AU - Javid,Asif, AU - Khan,Bilal Ahmad, AU - Ali,Anser, AU - Javed,Chaudhary Omer, Y1 - 2019/07/12/ PY - 2019/05/09/received PY - 2019/07/04/revised PY - 2019/07/11/accepted PY - 2019/7/19/pubmed PY - 2020/9/30/medline PY - 2019/7/19/entrez KW - 3-hydroxyflavones KW - 4-thioflavonols KW - AChE/BChE inhibitors KW - Cholinesterases KW - Flavonoids KW - Flavonols KW - Molecular docking studies KW - Sulfur compounds SP - 103124 EP - 103124 JF - Bioorganic chemistry JO - Bioorg Chem VL - 91 N2 - To explore new scaffolds for the treat of Alzheimer's disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1H-, 13C NMR) and mass spectrometry (EI-MS). All the derivatives (1-24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/31319297/Flavonols_and_4_thioflavonols_as_potential_acetylcholinesterase_and_butyrylcholinesterase_inhibitors:_Synthesis_structure_activity_relationship_and_molecular_docking_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(19)30745-X DB - PRIME DP - Unbound Medicine ER -