Perez-Areales_2017_Future.Med.Chem_9_965

Reference

Title : Design, synthesis and multitarget biological profiling of second-generation anti-Alzheimer rhein-huprine hybrids - Perez-Areales_2017_Future.Med.Chem_9_965
Author(s) : Perez-Areales FJ , Betari N , Viayna A , Pont C , Espargaro A , Bartolini M , De Simone A , Rinaldi Alvarenga JF , Perez B , Sabate R , Lamuela-Raventos RM , Andrisano V , Luque FJ , Munoz-Torrero D
Ref : Future Med Chem , 9 :965 , 2017
Abstract : AIM: Simultaneous modulation of several key targets of the pathological network of Alzheimer's disease (AD) is being increasingly pursued as a promising option to fill the critical gap of efficacious drugs against this condition. MATERIALS &
METHODS: A short series of compounds purported to hit multiple targets of relevance in AD has been designed, on the basis of their distinct basicities estimated from high-level quantum mechanical computations, synthesized, and subjected to assays of inhibition of cholinesterases, BACE-1, and Abeta42 and tau aggregation, of antioxidant activity, and of brain permeation.
RESULTS: Using, as a template, a lead rhein-huprine hybrid with an interesting multitarget profile, we have developed second-generation compounds, designed by the modification of the huprine aromatic ring. Replacement by [1,8]-naphthyridine or thieno[3,2-e]pyridine systems resulted in decreased, although still potent, acetylcholinesterase or BACE-1 inhibitory activities, which are more balanced relative to their Abeta42 and tau antiaggregating and antioxidant activities. CONCLUSION: Second-generation naphthyridine- and thienopyridine-based rhein-huprine hybrids emerge as interesting brain permeable compounds that hit several crucial pathogenic factors of AD.
ESTHER : Perez-Areales_2017_Future.Med.Chem_9_965
PubMedSearch : Perez-Areales_2017_Future.Med.Chem_9_965
PubMedID: 28632395

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Perez-Areales FJ, Betari N, Viayna A, Pont C, Espargaro A, Bartolini M, De Simone A, Rinaldi Alvarenga JF, Perez B, Sabate R, Lamuela-Raventos RM, Andrisano V, Luque FJ, Munoz-Torrero D (2017)
Design, synthesis and multitarget biological profiling of second-generation anti-Alzheimer rhein-huprine hybrids
Future Med Chem 9 :965

Perez-Areales FJ, Betari N, Viayna A, Pont C, Espargaro A, Bartolini M, De Simone A, Rinaldi Alvarenga JF, Perez B, Sabate R, Lamuela-Raventos RM, Andrisano V, Luque FJ, Munoz-Torrero D (2017)
Future Med Chem 9 :965