Design and discovery of anthranilamide derivatives as a potential treatment for neurodegenerative disorders via targeting cholinesterases and monoamine oxidases.
Autor: | Zaib S; Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore 54590, Pakistan. Electronic address: sumera.zaib@ucp.edu.pk., Khan I; Department of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester MI 7DN, UK. Electronic address: kimtiaz@hotmail.co.uk., Ali HS; Chemistry Research Laboratory, Department of Chemistry, the INEOS Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Younas MT; Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore 54590, Pakistan., Ibrar A; Department of Chemistry, Faculty of Physical and Applied Sciences, The University of Haripur, Haripur, KPK 22620, Pakistan. Electronic address: aliya.ibrar@uoh.edu.pk., Al-Odayni AB; Department of Restorative Dental Sciences, College of Dentistry, King Saud University, P.O. Box 60169, Riyadh 11545, Saudi Arabia., Al-Kahtani AA; Chemistry Department, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia. |
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Jazyk: | angličtina |
Zdroj: | International journal of biological macromolecules [Int J Biol Macromol] 2024 Jun; Vol. 272 (Pt 1), pp. 132748. Date of Electronic Publication: 2024 May 29. |
DOI: | 10.1016/j.ijbiomac.2024.132748 |
Abstrakt: | Neurodegenerative diseases with progressive cellular loss of the central nervous system and elusive disease etiology provide a continuous impetus to explore drug discovery programmes aiming at identifying robust and effective inhibitors of cholinesterase and monoamine oxidase enzymes. We herein present a concise library of anthranilamide derivatives involving a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction to install the diverse structural diversity required for the desired biological action. Using Ellman's method, cholinesterase inhibitory activity was performed against AChE and BuChE enzymes. In vitro assay results demonstrated that anthranilamides are potent inhibitors with remarkable potency. Compound 6k emerged as the lead candidate and dual inhibitor of both enzymes with IC Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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