Synthesis and biological evaluation of tacrine-thiadiazolidinone hybrids as dual acetylcholinesterase inhibitors.
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.
Dorronsoro
Isabel
I
Neuropharma, S.A. Avda. de la Industria 52, Tres Cantos, 28760 Madrid, Spain.
Alonso
Diana
D
Castro
Ana
A
del Monte
Maria
M
García-Palomero
Esther
E
Martínez
Ana
A
D000110:Acetylcholinesterase / Q000737:chemistry; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D011419:Propidium / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D013830:Thiadiazoles; D011419:Propidium; D013619:Tacrine; D000110:Acetylcholinesterase