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| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Bioorganic & medicinal chemistry | ||||
| Publisher: | Elsevier | ||||
| Volume: | 16 | ||||
| Number of Issue or Book Chapter: | 8 | ||||
| Page Range: | pp. 4252-4261 | ||||
| Date: | 2008 | ||||
| Additional Information (public): | CAN 149:464 1-3 Pharmacology 9000-81-1 (Acetylcholinesterase) Role: BSU (Biological study, unclassified), BIOL (Biological study) (hybrid mols. of quinazolinimines and lipoic acid as butyrylcholinesterase inhibitors with antioxidant properties); 1029034-02-3P; 1029034-03-4P; 1029034-04-5P; 1029034-05-6P; 1029034-06-7P; 1029034-07-8P; 1029034-08-9P; 1029034-09-0P; 1029034-10-3P; 1029034-11-4P; 1029034-12-5P; 1029034-13-6P; 1029034-14-7P; 1029034-15-8P Role: PAC (Pharmacological activity), SPN (Synthetic preparation), THU (Therapeutic use), BIOL (Biological study), PREP (Preparation), USES (Uses) (hybrid mols. of quinazolinimines and lipoic acid as butyrylcholinesterase inhibitors with antioxidant properties); 745837-16-5; 911366-60-4 Role: PAC (Pharmacological activity), THU (Therapeutic use), BIOL (Biological study), USES (Uses) (hybrid mols. of quinazolinimines and lipoic acid as butyrylcholinesterase inhibitors with antioxidant properties); 109-76-2 (1,3-Propanediamine); 110-60-1 (1,4-Butanediamine); 124-09-4 (1,6-Hexanediamine); 373-44-4 (1,8-Octanediamine); 462-94-2 (1,5-Pentanediamine); 646-19-5 (1,7-Heptanediamine); 1200-22-2 (Lipoic acid); 881890-07-9; 911366-48-8 Role: RCT (Reactant), RACT (Reactant or reagent) (hybrid mols. of quinazolinimines and lipoic acid as butyrylcholinesterase inhibitors with antioxidant properties); 9001-08-5 (Butyrylcholinesterase) Role: BSU (Biological study, unclassified), BIOL (Biological study) (inhibitors; hybrid mols. of quinazolinimines and lipoic acid as butyrylcholinesterase inhibitors with antioxidant properties) | ||||
| Institutions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) | ||||
| Identification Number: |
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| Keywords: | Antioxidants Cholinesterase inhibitors Structure-activity relationship (hybrid mols. of quinazolinimines and lipoic acid as butyrylcholinesterase inhibitors with antioxidant properties) butyrylcholinesterase inhibitor antioxidant quinazolinimine lipoate prepn SAR | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences 500 Science > 540 Chemistry & allied sciences | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 17237 |
Abstract
A set of hybrid mols. were synthesized out of lipoic acid, alpha ,w-diamines of different lengths serving as spacers, and cholinesterase (ChE) inhibiting [2,1-b]quinazolinimines. Depending on the length of the alkylene spacer the amide hybrids are inhibitors of acetylcholinesterase (AChE) with inhibitory activities of 0.5-4.6 micro M and inhibitors of butyrylcholinesterase (BChE) with activities ...
Abstract
A set of hybrid mols. were synthesized out of lipoic acid, alpha ,w-diamines of different lengths serving as spacers, and cholinesterase (ChE) inhibiting [2,1-b]quinazolinimines. Depending on the length of the alkylene spacer the amide hybrids are inhibitors of acetylcholinesterase (AChE) with inhibitory activities of 0.5-4.6 micro M and inhibitors of butyrylcholinesterase (BChE) with activities down to 5.7 nM, therefore greatly exceeding the inhibitory activities of the parent quinazolinimines by factors of up to 1000. Due to increasing activity at BChE with increasing length of the alkylene spacer .apprx.100-fold selectivity toward BChE is reached with a hepta- and an octamethylene spacer. Kinetic measurements reveal competitive and reversible inhibition of both ChEs by the hybrids. Furthermore, cell viability and antioxidant activity (using the ORAC-fluorescein assay) of several hybrids were evaluated, showing cytotoxicity at concns. from 3.7 to 10.2 micro M and antioxidant properties are in the range of 0.4-0.8 Trolox equiv. (lipoic acid = 0.6).
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