| Title : New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition - Malek_2019_J.Med.Chem_62_11416 |
| Author(s) : 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 , de los Rios C , Ismaili L |
| Ref : Journal of Medicinal Chemistry , 62 :11416 , 2019 |
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Abstract :
New tritarget small molecules combining Ca(2+) channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound 3p has been identified as a very promising lead, showing good Ca(2+) channels blockade activity (IC50 = 21 +/- 1 muM), potent affinity against hH3R (Ki = 565 +/- 62 nM), a moderate but selective hBuChE inhibition (IC50 = 7.83 +/- 0.10 muM), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lipopolysaccharide. |
| PubMedSearch : Malek_2019_J.Med.Chem_62_11416 |
| PubMedID: 31724859 |
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, de los Rios C, Ismaili L (2019)
New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition
Journal of Medicinal Chemistry
62 :11416
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, de los Rios C, Ismaili L (2019)
Journal of Medicinal Chemistry
62 :11416