New Dual Small Molecules for Alzheimer’s Disease Therapy Combining Histamine H3Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition

New tritarget small molecules combining Ca2+channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound 3phas been identified as a very promising lead, showing good Ca2+channels blockade activity (IC50= 21 ± 1 μM), potent affinity against hH3R (Ki= 565 ± 62 nM), a moderate but selective hBuChE inhibition (IC50= 7.83 ± 0.10 μM), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lipopolysaccharide.