New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H 3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition

New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H 3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition

New tritarget small molecules combining Ca channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound has been identified as a very promising lead, showing good Ca channels blockade activity (IC = 21 ± 1 μM), potent affinity against hH3R ( = 565...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of medicinal chemistry 2019-12, Vol.62 (24), p.11416-11422
Hauptverfasser: Malek, Rim, Arribas, Raquel L, Palomino-Antolin, Alejandra, Totoson, Perle, Demougeot, Celine, Kobrlova, Tereza, Soukup, Ondrej, Iriepa, Isabel, Moraleda, Ignacio, Diez-Iriepa, Daniel, Godyń, Justyna, Panek, Dawid, Malawska, Barbara, Głuch-Lutwin, Monika, Mordyl, Barbara, Siwek, Agata, Chabchoub, Fakher, Marco-Contelles, José, Kiec-Kononowicz, Katarzyna, Egea, Javier, de Los Ríos, Cristóbal, Ismaili, Lhassane
Format: Artikel
Sprache:eng
Schlagworte:
Chemical Sciences
Medicinal Chemistry
Organic chemistry
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:New tritarget small molecules combining Ca channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound has been identified as a very promising lead, showing good Ca channels blockade activity (IC = 21 ± 1 μM), potent affinity against hH3R ( = 565 ± 62 nM), a moderate but selective hBuChE inhibition (IC = 7.83 ± 0.10 μM), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lipopolysaccharide.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.9b00937