Lamuela-Raventos RM

References (2)

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

Title : Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties - Perez-Areales_2014_Bioorg.Med.Chem_22_5298
Author(s) : Perez-Areales FJ , Di Pietro O , Espargaro A , Vallverdu-Queralt A , Galdeano C , Ragusa IM , Viayna E , Guillou C , Clos MV , Perez B , Sabate R , Lamuela-Raventos RM , Luque FJ , Munoz-Torrero D
Ref : Bioorganic & Medicinal Chemistry , 22 :5298 , 2014
Abstract : Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaol-huprine hybrids, purported to hit several key targets involved in Alzheimer's disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS(+), DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Abeta42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Abeta42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaol-huprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads.
ESTHER : Perez-Areales_2014_Bioorg.Med.Chem_22_5298
PubMedSearch : Perez-Areales_2014_Bioorg.Med.Chem_22_5298
PubMedID: 25156301