title: Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetylcholinesterase inhibitory and antioxidant properties.
abstract: Tacrine and melatonin are well-known drugs with activities as an acetylcholinesterase (AChE) inhibitor and free radical scavenger, respectively. In this work, we report new hybrids of both drugs that display higher in vitro properties than the sum of their parts. As selective inhibitors of human AChE, their IC(50) values range from sub-nanomolar to picomolar. They exhibit a higher oxygen radical absorbance capacity than does melatonin and are predicted to be able to cross the blood-brain barrier to reach their targets in the central nervous system.
authors.affiliation: Instituto de Química Médica (CSIC), 28006 Madrid, Spain. IsabelRguez@iqm.csic.es
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Rodríguez-Franco
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Fernández-Bachiller
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez
authors.forename: Blanca
authors.initials: B
authors.lastname: Hernández-Ledesma
authors.forename: Begoña
authors.initials: B
authors.lastname: Bartolomé
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008550:Melatonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D010539:Permeability; D013329:Structure-Activity Relationship; D013552:Swine; D013619:Tacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D014020:Tissue Extracts / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D014020:Tissue Extracts; D013619:Tacrine; D000110:Acetylcholinesterase; D008550:Melatonin