Munoz-Ruiz_2005_J.Med.Chem_48_7223

Reference

Title : Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer's disease - Munoz-Ruiz_2005_J.Med.Chem_48_7223
Author(s) : Munoz-Ruiz P , Rubio L , Garcia-Palomero E , Dorronsoro I , del Monte-Millan M , Valenzuela R , Usan P , de Austria C , Bartolini M , Andrisano V , Bidon-Chanal A , Orozco M , Luque FJ , Medina M , Martinez A
Ref : Journal of Medicinal Chemistry , 48 :7223 , 2005
Abstract : New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as new potent drugs that may simultaneously alleviate cognitive deficits and behave as disease-modifying agents by inhibiting the beta-amyloid (A beta) peptide aggregation through binding to both catalytic and peripheral sites of the enzyme. Particularly, compounds 5 and 6 emerged as the most potent heterodimers reported so far, displaying IC50 values for AChE inhibition of 20 and 60 pM, respectively. More importantly, these dual AChE inhibitors inhibit the AChE-induced A beta peptide aggregation with IC50 values 1 order of magnitude lower than that of propidium, thus being the most potent derivatives with this activity reported up to date. We therefore conclude that these compounds are very promising disease-modifying agents for the treatment of Alzheimer's disease (AD).
ESTHER : Munoz-Ruiz_2005_J.Med.Chem_48_7223
PubMedSearch : Munoz-Ruiz_2005_J.Med.Chem_48_7223
PubMedID: 16279781

Related information

Inhibitor NP61

Citations formats

Munoz-Ruiz P, Rubio L, Garcia-Palomero E, Dorronsoro I, del Monte-Millan M, Valenzuela R, Usan P, de Austria C, Bartolini M, Andrisano V, Bidon-Chanal A, Orozco M, Luque FJ, Medina M, Martinez A (2005)
Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer's disease
Journal of Medicinal Chemistry 48 :7223

Munoz-Ruiz P, Rubio L, Garcia-Palomero E, Dorronsoro I, del Monte-Millan M, Valenzuela R, Usan P, de Austria C, Bartolini M, Andrisano V, Bidon-Chanal A, Orozco M, Luque FJ, Medina M, Martinez A (2005)
Journal of Medicinal Chemistry 48 :7223

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    [paper] => Munoz-Ruiz_2005_J.Med.Chem_48_7223
    [author] => Munoz-Ruiz P || Rubio L || Garcia-Palomero E || Dorronsoro I || del Monte-Millan M || Valenzuela R || Usan P || de Austria C || Bartolini M || Andrisano V || Bidon-Chanal A || Orozco M || Luque FJ || Medina M || Martinez A
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    [title] => Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer's disease
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            [content] => New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as new potent drugs that may simultaneously alleviate cognitive deficits and behave as disease-modifying agents by inhibiting the beta-amyloid (A beta) peptide aggregation through binding to both catalytic and peripheral sites of the enzyme. Particularly, compounds 5 and 6 emerged as the most potent heterodimers reported so far, displaying IC50 values for AChE inhibition of 20 and 60 pM, respectively. More importantly, these dual AChE inhibitors inhibit the AChE-induced A beta peptide aggregation with IC50 values 1 order of magnitude lower than that of propidium, thus being the most potent derivatives with this activity reported up to date. We therefore conclude that these compounds are very promising disease-modifying agents for the treatment of Alzheimer's disease (AD).
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