Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetylcholinesterase inhibitory and antioxidant properties.
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.
Rodríguez-Franco
María Isabel
MI
Instituto de Química Médica (CSIC), 28006 Madrid, Spain. IsabelRguez@iqm.csic.es
Fernández-Bachiller
María Isabel
MI
Pérez
Concepción
C
Hernández-Ledesma
Blanca
B
Bartolomé
Begoña
B
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
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D014020:Tissue Extracts; D013619:Tacrine; D000110:Acetylcholinesterase; D008550:Melatonin