Tags

Type your tag names separated by a space and hit enter

Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione derivatives as dual-binding site acetylcholinesterase inhibitors.
Arch Pharm (Weinheim). 2012 Jul; 345(7):509-16.AP

Abstract

A new series of 2-(diethylaminoalkyl)-isoindoline-1,3-dione derivatives intended as dual binding site cholinesterase inhibitors were designed using molecular modeling and evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and the formation of the β-amyloid (Aβ) plaques. For AChE inhibitory activity, the spectrophotometric method of Ellman and the electrophoretically mediated microanalysis assay were used, giving good results. Most of the synthesized compounds had AChE inhibitory activity with IC(50) values ranging from IC(50) = 0.9 to 19.5 µM and weak Aβ anti-aggregation inhibitory activity. These results support the outcome of docking studies which tested compounds targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The most promising selective AChE inhibitors are compounds 10 (IC(50) = 1.2 µM) and 11 (IC(50) = 1.1 µM), with 6-7 methylene chains, which also inhibit Aβ fibril formation.

Authors+Show Affiliations

Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Kraków, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22467516

Citation

Ignasik, Michalina, et al. "Design, Synthesis and Evaluation of Novel 2-(aminoalkyl)-isoindoline-1,3-dione Derivatives as Dual-binding Site Acetylcholinesterase Inhibitors." Archiv Der Pharmazie, vol. 345, no. 7, 2012, pp. 509-16.
Ignasik M, Bajda M, Guzior N, et al. Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione derivatives as dual-binding site acetylcholinesterase inhibitors. Arch Pharm (Weinheim). 2012;345(7):509-16.
Ignasik, M., Bajda, M., Guzior, N., Prinz, M., Holzgrabe, U., & Malawska, B. (2012). Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione derivatives as dual-binding site acetylcholinesterase inhibitors. Archiv Der Pharmazie, 345(7), 509-16. https://doi.org/10.1002/ardp.201100423
Ignasik M, et al. Design, Synthesis and Evaluation of Novel 2-(aminoalkyl)-isoindoline-1,3-dione Derivatives as Dual-binding Site Acetylcholinesterase Inhibitors. Arch Pharm (Weinheim). 2012;345(7):509-16. PubMed PMID: 22467516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione derivatives as dual-binding site acetylcholinesterase inhibitors. AU - Ignasik,Michalina, AU - Bajda,Marek, AU - Guzior,Natalia, AU - Prinz,Michaela, AU - Holzgrabe,Ulrike, AU - Malawska,Barbara, Y1 - 2012/03/30/ PY - 2011/11/23/received PY - 2012/01/23/revised PY - 2012/02/16/accepted PY - 2012/4/3/entrez PY - 2012/4/3/pubmed PY - 2012/12/27/medline SP - 509 EP - 16 JF - Archiv der Pharmazie JO - Arch Pharm (Weinheim) VL - 345 IS - 7 N2 - A new series of 2-(diethylaminoalkyl)-isoindoline-1,3-dione derivatives intended as dual binding site cholinesterase inhibitors were designed using molecular modeling and evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and the formation of the β-amyloid (Aβ) plaques. For AChE inhibitory activity, the spectrophotometric method of Ellman and the electrophoretically mediated microanalysis assay were used, giving good results. Most of the synthesized compounds had AChE inhibitory activity with IC(50) values ranging from IC(50) = 0.9 to 19.5 µM and weak Aβ anti-aggregation inhibitory activity. These results support the outcome of docking studies which tested compounds targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The most promising selective AChE inhibitors are compounds 10 (IC(50) = 1.2 µM) and 11 (IC(50) = 1.1 µM), with 6-7 methylene chains, which also inhibit Aβ fibril formation. SN - 1521-4184 UR - https://www.unboundmedicine.com/medline/citation/22467516/Design_synthesis_and_evaluation_of_novel_2__aminoalkyl__isoindoline_13_dione_derivatives_as_dual_binding_site_acetylcholinesterase_inhibitors_ L2 - https://doi.org/10.1002/ardp.201100423 DB - PRIME DP - Unbound Medicine ER -