Synthesis and biological assessment of KojoTacrines as new agents for Alzheimer’s disease therapy
Autor: | Youssef Dgachi, Hélène Martin, Rim Malek, Daniel Jun, Jana Janockova, Vendula Sepsova, Ondrej Soukup, Isabel Iriepa, Ignacio Moraleda, Emna Maalej, M. Carmo Carreiras, Bernard Refouvelet, Fakher Chabchoub, José Marco-Contelles, Lhassane Ismaili |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: | |
Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 34, Iss 1, Pp 163-170 (2019) |
Druh dokumentu: | article |
ISSN: | 1475-6366 1475-6374 14756366 |
DOI: | 10.1080/14756366.2018.1538136 |
Popis: | In view of the multifactorial nature of Alzheimer’s disease (AD), multitarget small molecules (MTSM) represent the most potent and attractive therapeutic strategy to design new drugs for Alzheimer’s disease therapy. The new MTSM KojoTacrines (KTs) were designed and synthesized by juxtaposition of selected pharmacophoric motifs from kojic acid and tacrine. Among them, 11-amino-2-(hydroxymethyl)-12-(3-methoxyphenyl)-7,9,10,12-tetrahydropyrano [2',3':5,6] pyrano[2,3-b]quinolin-4(8H)-one (KT2d) was identified as less-hepatotoxic than tacrine, at higher concentration, a moderate, but selective human acetylcholinesterase inhibitor (IC50 = 4.52 ± 0.24 µM), as well as an antioxidant agent (TE = 4.79) showing significant neuroprotection against Aβ1–40 at 3 µM and 10 µM concentrations. Consequently, KT2d is a potential new hit-ligand for AD therapy for further biological exploration. |
Databáze: | Directory of Open Access Journals |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |