New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H-3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition
| Affiliation auteurs | !!!! Error affiliation !!!! |
| Titre | New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H-3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition |
| Type de publication | Journal Article |
| Year of Publication | 2019 |
| Auteurs | Malek R, Arribas RL, Palomino-Antolin A, Totoson P, Demougeot C, Kobrlova T, Soukup O, Iriepa I, Moraleda I, Diez-Iriepa D, Godyn J, Panek D, Malawska B, Gluch-Lutwin M, Mordyl B, Siwek A, Chabchoub F, Marco-Contelles J, Kiec-Kononowicz K, Egea J, Rios Cde los, Ismaili L |
| Journal | JOURNAL OF MEDICINAL CHEMISTRY |
| Volume | 62 |
| Pagination | 11416-11422 |
| Date Published | DEC 26 |
| Type of Article | Article |
| ISSN | 0022-2623 |
| Résumé | 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. |
| DOI | 10.1021/acs.jmedchem.9b00937 |