New dual small molecules for Alzheimer's disease therapy combining histamine H-3 receptor (H3R) antagonism and calcium channels blockade with additional Cholinesterase inhibition
2019
Abstract
New tritarget small molecules combining Ca2+ channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound 3p has been identified as a very promising lead, showing good Ca2+ channels blockade activity (IC50 = 21 +/- 1 mu M), potent affinity against hH3R (K-i = 565 +/- 62 nM), a moderate but selective hBuChE inhibition (IC50 = 7.83 +/- 0.10 mu M), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lip opolysaccharide.