Several years ago, a short series of racemic huprine-tacrine hybrids was developed as a new class of dual binding site acetylcholinesterase (AChE) inhibitors. These compounds consisted of: i) a unit of huprine Y, a compound with one of the highest affinities for the active site of AChE yet reported, ii) a unit of tacrine, a compound with known affinity for the peripheral site of AChE, and iii) a linker of appropriate length to allow simultaneous binding to both the active and peripheral sites of the enzyme. Recently, the series of huprine-tacrine hybrids has been extended with the synthesis of shorter and longer homologues. Also, the two enantiomers of two of the most potent racemic huprine-tacrine hybrids have been independently synthesized from readily available (-)- and (+)-huprine Y, and their binding mode has been studied by molecular dynamics simulations. Moreover, additional pharmacological and pharmacokinetic studies have been undertaken. Among other properties, some huprine-tacrine hybrids have been shown to be able to significantly inhibit the AChE-induced A-beta and prion peptide aggregation, two key pathogenic processes involved in AD and in prion diseases, and seem to be able to cross the blood-brain barrier.

HUPRINETACRINE HYBRIDS AS A NOVEL FAMILY OF MULTI-TARGET DRUG CANDIDATES AGAINST ALZHEIMER’S AND PRION DISEASES / D. Muñoz-Torrero; P. Camps; X. Formosa; C. Galdeano; E. Viayna; A. Badia; M. Victòria Clos; M. Pera; M. Ratia; B. Pérez Fernández; M. Bartolini; F. Mancini; V. Andrisano; G. C. González-Muñoz; M. I. Rodríguez-Franco; L. Rivail; F. J. Luque. - STAMPA. - (2009), pp. 75-75. (Intervento presentato al convegno 10th International Meeting on Cholinesterases tenutosi a Šibenik, Croatia nel 20-25 September 2009).

HUPRINETACRINE HYBRIDS AS A NOVEL FAMILY OF MULTI-TARGET DRUG CANDIDATES AGAINST ALZHEIMER’S AND PRION DISEASES

BARTOLINI, MANUELA;MANCINI, FRANCESCA;ANDRISANO, VINCENZA;
2009

Abstract

Several years ago, a short series of racemic huprine-tacrine hybrids was developed as a new class of dual binding site acetylcholinesterase (AChE) inhibitors. These compounds consisted of: i) a unit of huprine Y, a compound with one of the highest affinities for the active site of AChE yet reported, ii) a unit of tacrine, a compound with known affinity for the peripheral site of AChE, and iii) a linker of appropriate length to allow simultaneous binding to both the active and peripheral sites of the enzyme. Recently, the series of huprine-tacrine hybrids has been extended with the synthesis of shorter and longer homologues. Also, the two enantiomers of two of the most potent racemic huprine-tacrine hybrids have been independently synthesized from readily available (-)- and (+)-huprine Y, and their binding mode has been studied by molecular dynamics simulations. Moreover, additional pharmacological and pharmacokinetic studies have been undertaken. Among other properties, some huprine-tacrine hybrids have been shown to be able to significantly inhibit the AChE-induced A-beta and prion peptide aggregation, two key pathogenic processes involved in AD and in prion diseases, and seem to be able to cross the blood-brain barrier.
2009
10th International Meeting on Cholinesterases, Programme and Abstracts
75
75
HUPRINETACRINE HYBRIDS AS A NOVEL FAMILY OF MULTI-TARGET DRUG CANDIDATES AGAINST ALZHEIMER’S AND PRION DISEASES / D. Muñoz-Torrero; P. Camps; X. Formosa; C. Galdeano; E. Viayna; A. Badia; M. Victòria Clos; M. Pera; M. Ratia; B. Pérez Fernández; M. Bartolini; F. Mancini; V. Andrisano; G. C. González-Muñoz; M. I. Rodríguez-Franco; L. Rivail; F. J. Luque. - STAMPA. - (2009), pp. 75-75. (Intervento presentato al convegno 10th International Meeting on Cholinesterases tenutosi a Šibenik, Croatia nel 20-25 September 2009).
D. Muñoz-Torrero; P. Camps; X. Formosa; C. Galdeano; E. Viayna; A. Badia; M. Victòria Clos; M. Pera; M. Ratia; B. Pérez Fernández; M. Bartolini; F. Mancini; V. Andrisano; G. C. González-Muñoz; M. I. Rodríguez-Franco; L. Rivail; F. J. Luque
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/77769
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