1. Synthesis and biological evaluation of tacrine-thiadiazolidinone hybrids as dual acetylcholinesterase inhibitors.
- Author
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Dorronsoro I, Alonso D, Castro A, del Monte M, García-Palomero E, and Martínez A
- Subjects
- Acetylcholinesterase chemistry, Animals, Binding, Competitive, Cattle, Cell Line, Tumor, Cholinesterase Inhibitors chemistry, Cholinesterase Inhibitors pharmacology, Erythrocytes drug effects, Erythrocytes enzymology, Humans, In Vitro Techniques, Propidium pharmacology, Structure-Activity Relationship, Tacrine chemistry, Tacrine pharmacology, Thiadiazoles chemistry, Thiadiazoles pharmacology, Cholinesterase Inhibitors chemical synthesis, Tacrine chemical synthesis, Thiadiazoles chemical synthesis
- Abstract
The synthesis of tacrine-thiadiazolidinone hybrids is described. These compounds are designed as dual acetylcholinesterase inhibitors binding simultaneously to the peripheral and catalytic sites of the enzyme. All tested compounds exhibit significant AChE inhibitory activity. Competition assays using propidium as reference of selective ligand for the peripheral anionic site on acetylcholinesterase indicates the influence of the designed compounds over the peripheral site. They can be considered as new leads in the optimization of Alzheimer's disease modifying agents.
- Published
- 2005
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