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Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation.
Bioorg Med Chem. 2016 05 15; 24(10):2352-9.BM

Abstract

A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.

Authors+Show Affiliations

Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, PR China.Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, PR China.Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, PR China. Electronic address: qinhuali@whut.edu.cn.Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor, Malaysia.Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. Electronic address: snab@ukm.edu.my.

Pub Type(s)

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

Language

eng

PubMed ID

27083471

Citation

Zha, Gao-Feng, et al. "Biological Evaluation of Synthetic Α,β-unsaturated Carbonyl Based Cyclohexanone Derivatives as Neuroprotective Novel Inhibitors of Acetylcholinesterase, Butyrylcholinesterase and Amyloid-β Aggregation." Bioorganic & Medicinal Chemistry, vol. 24, no. 10, 2016, pp. 2352-9.
Zha GF, Zhang CP, Qin HL, et al. Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Bioorg Med Chem. 2016;24(10):2352-9.
Zha, G. F., Zhang, C. P., Qin, H. L., Jantan, I., Sher, M., Amjad, M. W., Hussain, M. A., Hussain, Z., & Bukhari, S. N. (2016). Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Bioorganic & Medicinal Chemistry, 24(10), 2352-9. https://doi.org/10.1016/j.bmc.2016.04.015
Zha GF, et al. Biological Evaluation of Synthetic Α,β-unsaturated Carbonyl Based Cyclohexanone Derivatives as Neuroprotective Novel Inhibitors of Acetylcholinesterase, Butyrylcholinesterase and Amyloid-β Aggregation. Bioorg Med Chem. 2016 05 15;24(10):2352-9. PubMed PMID: 27083471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. AU - Zha,Gao-Feng, AU - Zhang,Cheng-Pan, AU - Qin,Hua-Li, AU - Jantan,Ibrahim, AU - Sher,Muhammad, AU - Amjad,Muhammad Wahab, AU - Hussain,Muhammad Ajaz, AU - Hussain,Zahid, AU - Bukhari,Syed Nasir Abbas, Y1 - 2016/04/08/ PY - 2016/01/16/received PY - 2016/03/29/revised PY - 2016/04/07/accepted PY - 2016/4/17/entrez PY - 2016/4/17/pubmed PY - 2017/7/6/medline KW - Alzheimer’s disease KW - Dementia KW - Neurodegeneration KW - Neuroprotection SP - 2352 EP - 9 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 24 IS - 10 N2 - A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/27083471/Biological_evaluation_of_synthetic_αβ_unsaturated_carbonyl_based_cyclohexanone_derivatives_as_neuroprotective_novel_inhibitors_of_acetylcholinesterase_butyrylcholinesterase_and_amyloid_β_aggregation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(16)30249-8 DB - PRIME DP - Unbound Medicine ER -