Houssem Boulebd1, Lhassane Ismaili2, Helene Martin3, Alexandre Bonet3, Mourad Chioua4, José Marco Contelles4, Ali Belfaitah1. 1. Laboratoire des Produits Naturels d'Origine Végétale et de Synthèse Organique. Faculté des Sciences Exactes, Campus de Chaabat Ersas, Université des frères Mentouri-Constantine. Constantine 25000, Algeria. 2. Laboratoire de Chimie Organique et Thérapeutique, Neurosciences intégratives et cliniques EA 481, UFR SMP, 19 rue Ambroise Paré, Université Bourgogne Franche-Comté, F-25000 Besançon Cedex, France. 3. PEPITE EA4267, laboratoire de Toxicologie Cellulaire, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France. 4. Laboratory of Medicinal Chemistry, (Instituto de Química Orgánica General, CSIC) C/Juan de la Cierva 3, 28006-Madrid, Spain.
Abstract
AIM: Due to the multifactorial nature of Alzheimer's disease, there is an urgent search for new more efficient, multitarget-directed drugs. RESULTS: This paper describes the synthesis, antioxidant and in vitro biological evaluation of ten (benz)imidazopyridino tacrines (7-16), showing less toxicity than tacrine at high doses, and potent cholinesterase inhibitory capacity, in the low micromolar range. Among them, compound 10 is a nonhepatotoxic tacrine at 1000 mM, showing moderate, but totally selective electric eel acetylcholinesterase inhibition, whereas molecule 16 is twofold less toxic than tacrine at 1000 μM, showing moderate and almost equipotent inhibition for electric eel acetylcholinesterase and equine butyrylcholinesterase. CONCLUSION: (Benz)imidazopyridino tacrines (7-16) have been identified as a new and promising type of tacrines for the potential treatment of Alzheimer's disease.
AIM: Due to the multifactorial nature of Alzheimer's disease, there is an urgent search for new more efficient, multitarget-directed drugs. RESULTS: This paper describes the synthesis, antioxidant and in vitro biological evaluation of ten (benz)imidazopyridino tacrines (7-16), showing less toxicity than tacrine at high doses, and potent cholinesterase inhibitory capacity, in the low micromolar range. Among them, compound 10 is a nonhepatotoxic tacrine at 1000 mM, showing moderate, but totally selective electric eel acetylcholinesterase inhibition, whereas molecule 16 is twofold less toxic than tacrine at 1000 μM, showing moderate and almost equipotent inhibition for electric eel acetylcholinesterase and equine butyrylcholinesterase. CONCLUSION:(Benz)imidazopyridino tacrines (7-16) have been identified as a new and promising type of tacrines for the potential treatment of Alzheimer's disease.