| Title : New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol - Mao_2014_Org.Biomol.Chem_12_5936 |
| Author(s) : Mao F , Yan J , Li J , Jia X , Miao H , Sun Y , Huang L , Li X |
| Ref : Org Biomol Chem , 12 :5936 , 2014 |
| Abstract : Alzheimer's disease (AD) is currently one of the most difficult and challenging diseases to treat. Based on the 'multi-target-directed ligands' (MTDLs) strategy, we designed and synthesised a series of new compounds against AD by combining the pharmacophores of resveratrol and clioquinol. The results of biological activity tests showed that the hybrids exhibited excellent MTDL properties: a significant ability to inhibit self-induced beta-amyloid (Abeta) aggregation and copper(II)-induced Abeta aggregation, potential antioxidant behaviour (ORAC-FL value of 0.9-3.2 Trolox equivalents) and biometal chelation. Among these compounds, (E)-5-(4-hydroxystyryl)quinoline-8-ol (10c) showed the most potent ability to inhibit self-induced Abeta aggregation (IC50 = 8.50 microM) and copper(II)-induced Abeta aggregation and to disassemble the well-structured Abeta fibrils generated by self- and copper(II)-induced Abeta aggregation. Note that 10c could also control Cu(I/II)-triggered hydroxyl radical (OH) production by halting copper redox cycling via metal complexation, as confirmed by a Cu-ascorbate redox system assay. Importantly, 10c did not show acute toxicity in mice at doses of up to 2000 mg kg1 and was able to cross the blood-brain barrier (BBB), according to a parallel artificial membrane permeation assay. These results indicate that compound 10c is a promising multifunctional compound for the development of novel drugs for AD. |
| ESTHER : Mao_2014_Org.Biomol.Chem_12_5936 |
| PubMedSearch : Mao_2014_Org.Biomol.Chem_12_5936 |
| PubMedID: 24986600 |
Mao F, Yan J, Li J, Jia X, Miao H, Sun Y, Huang L, Li X (2014)
New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol
Org Biomol Chem
12 :5936
Mao F, Yan J, Li J, Jia X, Miao H, Sun Y, Huang L, Li X (2014)
Org Biomol Chem
12 :5936