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Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and Molecular Docking Studies.
Med Chem. 2018; 14(8):809-817.MC

Abstract

BACKGROUND

Alzheimer's Disease (AD) is the leading cause of dementia among the aging population. This devastating disorder is generally associated with the gradual memory loss, specified by a decrease of acetylcholine level in the cortex hippocampus of the brain due to hyperactivation of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)).

OBJECTIVE

Therefore, inactivation of AChE and BChE by inhibitors can increase the acetylcholine level and hence may be an encouraging strategy for the treatment of AD and related neurological problems.

METHOD

In this contribution, two series of chromenone-based derivatives were tested by Ellmann's calorimetric method for AChE and BChE inhibition.

RESULTS

All the compounds showed inhibitory activity against cholinesterases and some of them exhibited dual inhibition of AChE as well as BChE. The most potent inhibitor of AChE was 2l having an IC50 value of 0.08 ± 0.03 µM, while 3q inhibited the BChE with an IC50 value of 0.04 ± 0.01 µM. In case of dual inhibition, 3h showed an inhibitory concentration of 0.15 ± 0.01 µM for AChE, and 0.09 ± 0.01 µM for BChE. Molecular docking studies were performed to explore the probable binding modes of the most potent dual inhibitors.

CONCLUSION

It can be hypothesized that the inhibitors are able to target cholinesterase pathways and may emerge as a suitable outset for the further development process.

Authors+Show Affiliations

Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, Abbottabad-22060, Pakistan.Institut für Chemie, Universität Rostock, Albert Einstein Str. 3A, 18059 Rostock, Germany.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, Abbottabad-22060, Pakistan.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, Abbottabad-22060, Pakistan.Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich- Wilhelms-Universität, Dahlmannstr. 2, D-53113 Bonn, Germany.Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich- Wilhelms-Universität, Dahlmannstr. 2, D-53113 Bonn, Germany.Institut für Chemie, Universität Rostock, Albert Einstein Str. 3A, 18059 Rostock, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29473519

Citation

Iqbal, Jamshed, et al. "Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and Molecular Docking Studies." Medicinal Chemistry (Shariqah (United Arab Emirates)), vol. 14, no. 8, 2018, pp. 809-817.
Iqbal J, Abbasi MSA, Zaib S, et al. Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and Molecular Docking Studies. Med Chem. 2018;14(8):809-817.
Iqbal, J., Abbasi, M. S. A., Zaib, S., Afridi, S., Furtmann, N., Bajorath, J., & Langer, P. (2018). Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and Molecular Docking Studies. Medicinal Chemistry (Shariqah (United Arab Emirates)), 14(8), 809-817. https://doi.org/10.2174/1573406414666180222091833
Iqbal J, et al. Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and Molecular Docking Studies. Med Chem. 2018;14(8):809-817. PubMed PMID: 29473519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and Molecular Docking Studies. AU - Iqbal,Jamshed, AU - Abbasi,Muhammad S A, AU - Zaib,Sumera, AU - Afridi,Saifullah, AU - Furtmann,Norbert, AU - Bajorath,Jürgen, AU - Langer,Peter, PY - 2017/09/16/received PY - 2018/01/27/revised PY - 2018/01/29/accepted PY - 2018/2/24/pubmed PY - 2019/3/6/medline PY - 2018/2/24/entrez KW - Alzheimer's disease KW - amino acid KW - cholinesterase inhibitor KW - chromenone derivatives KW - chromosome KW - molecular docking. SP - 809 EP - 817 JF - Medicinal chemistry (Shariqah (United Arab Emirates)) JO - Med Chem VL - 14 IS - 8 N2 - BACKGROUND: Alzheimer's Disease (AD) is the leading cause of dementia among the aging population. This devastating disorder is generally associated with the gradual memory loss, specified by a decrease of acetylcholine level in the cortex hippocampus of the brain due to hyperactivation of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)). OBJECTIVE: Therefore, inactivation of AChE and BChE by inhibitors can increase the acetylcholine level and hence may be an encouraging strategy for the treatment of AD and related neurological problems. METHOD: In this contribution, two series of chromenone-based derivatives were tested by Ellmann's calorimetric method for AChE and BChE inhibition. RESULTS: All the compounds showed inhibitory activity against cholinesterases and some of them exhibited dual inhibition of AChE as well as BChE. The most potent inhibitor of AChE was 2l having an IC50 value of 0.08 ± 0.03 µM, while 3q inhibited the BChE with an IC50 value of 0.04 ± 0.01 µM. In case of dual inhibition, 3h showed an inhibitory concentration of 0.15 ± 0.01 µM for AChE, and 0.09 ± 0.01 µM for BChE. Molecular docking studies were performed to explore the probable binding modes of the most potent dual inhibitors. CONCLUSION: It can be hypothesized that the inhibitors are able to target cholinesterase pathways and may emerge as a suitable outset for the further development process. SN - 1875-6638 UR - https://www.unboundmedicine.com/medline/citation/29473519/Identification_of_New_Chromenone_Derivatives_as_Cholinesterase_Inhibitors_and_Molecular_Docking_Studies_ L2 - http://www.eurekaselect.com/160018/article DB - PRIME DP - Unbound Medicine ER -