| Title : Novel Vilazodone-Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation - Li_2017_ACS.Chem.Neurosci_8_2708 |
| Author(s) : Li X , Wang H , Xu Y , Liu W , Gong Q , Wang W , Qiu X , Zhu J , Mao F , Zhang H , Li J |
| Ref : ACS Chem Neurosci , 8 :2708 , 2017 |
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Abstract :
Depression is one of the most frequent psychiatric complications of Alzheimer's disease (AD), affecting up to 50% of the patients. A novel series of hybrid molecules were designed and synthesized by combining the pharmacophoric features of vilazodone and tacrine as potential multitarget-directed ligands for the treatment of AD with depression. In vitro biological assays were conducted to evaluate the compounds; among the 30 hybrids, compound 1e showed relatively balanced profiles between acetylcholinesterase inhibition (IC50 = 3.319 +/- 0.708 muM), 5-HT1A agonist (EC50 = 107 +/- 37 nM), and 5-HT reuptake inhibition (IC50 = 76.3 +/- 33 nM). Compound 1e displayed tolerable hepatotoxicity and moderate hERG inhibition activity, and could penetrate the blood-brain barrier in vivo. Furthermore, an oral intake of 30 mg/kg 1e.HCl could significantly improve the cognitive function of scopolamine-induced amnesia mice and alleviate the depressive symptom in tail suspension test. The effectivity of 1e validates the rationality of our design strategy. |
| PubMedSearch : Li_2017_ACS.Chem.Neurosci_8_2708 |
| PubMedID: 28872831 |
Li X, Wang H, Xu Y, Liu W, Gong Q, Wang W, Qiu X, Zhu J, Mao F, Zhang H, Li J (2017)
Novel Vilazodone-Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation
ACS Chem Neurosci
8 :2708
Li X, Wang H, Xu Y, Liu W, Gong Q, Wang W, Qiu X, Zhu J, Mao F, Zhang H, Li J (2017)
ACS Chem Neurosci
8 :2708