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Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease
Imen Dakhlaoui1,2, Paul J Bernard1, Diana Pietrzak3
1Laboratoire LINC UR 481, Pôle de Chimie Médicinale, Université de Franche-Comté, F-25000 Besançon, France.
Abstract:
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.
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