5396-25-8Relevant articles and documents
Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors
Najafi, Zahra,Mahdavi, Mohammad,Saeedi, Mina,Karimpour-Razkenari, Elahe,Asatouri, Raymond,Vafadarnejad, Fahimeh,Moghadam, Farshad Homayouni,Khanavi, Mahnaz,Sharifzadeh, Mohammad,Akbarzadeh, Tahmineh
, p. 1200 - 1212 (2017)
A new series of tacrine-1,2,3-triazole hybrids were designed, synthesized, and evaluated as potent dual cholinesterase inhibitors. Most of synthesized compounds showed good in vitro inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 7-chloro-N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5l) was found to be the most potent anti-AChE derivative (IC50= 0.521 μM) and N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5j) demonstrated the best anti-BChE activity (IC50= 0.055 μM). In vivo studies of compound 5l in Morris water maze task confirmed memory improvement in scopolamine-induced impairment. Also, molecular modeling and kinetic studies showed that compounds 5l and 5j bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CS) of the AChE and BChE.
Synthesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of AD
Digiacomo, Maria,Chen, Ziwei,Wang, Shengnan,Lapucci, Annalina,Macchia, Marco,Yang, Xiaohong,Chu, Jiaqi,Han, Yifan,Pi, Rongbiao,Rapposelli, Simona
, p. 807 - 810 (2015)
A novel series of tacrine derivatives were designed and synthesized by combining caffeic acid (CA), ferulic acid (FA) and lipoic acid (LA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to
ACRIDIN-9-YL-AMINE, QUINOLIN-9-YL-AMINE, 1 -AMINO-9H-THIOXANTHENE-9-ONE AND BENZO[B][1,5]NAPHTHYRI DIN-10-YL-AMINE DERIVATIVES AS AUTOPHAGY INHIBITORS FOR TREATING CANCER
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Paragraph 0254; 0314, (2021/07/17)
This disclosure provides a cridin-9-yl-amine, quinolin-9-yl-amine, 1- amino-9H-thioxanthene-9-one and benzo[b][l,5]naphthyridin-10- yl-amine derivatives and structurally related compounds for use as autophagy inhibitors for treating cancer. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 77 to 155; examples 1 to 22; compound A; compounds 1 to 21; tables 1 to 3).
A tacrine-tetrahydroquinoline heterodimer potently inhibits acetylcholinesterase activity and enhances neurotransmission in mice
Ip, Fanny C.F.,Fu, Guangmiao,Yang, Fengzhi,Kang, Fangyuan,Sun, Peiran,Ling, Choi Ying,Cheung, Kit,Xie, Fangzhou,Hu, Yueqing,Fu, Lei,Ip, Nancy Y.
supporting information, (2021/09/18)
Cholinergic neurons are ubiquitous and involved in various higher brain functions including learning and memory. Patients with Alzheimer's disease exhibit significant dysfunction and loss of cholinergic neurons. Meanwhile, such cholinergic deficits can be potentially relieved pharmacologically by increasing acetylcholine. Acetylcholinesterase (AChE) inhibitors have been used to improve cholinergic transmission in the brain for two decades and have proven effective for alleviating symptoms in the early stages of Alzheimer's disease. Therefore, the search for AChE inhibitors for drug development is ongoing. The enzymatic pocket of AChE has long been the target of several drug designs over the last two decades. The peripheral and catalytic sites of AChE are simultaneously bound by several dimeric molecules, enabling more-efficient inhibition. Here, we used 6-chlorotacrine and the tetrahydroquinolone moiety of huperzine A to design and synthesize a series of heterodimers that inhibit AChE at nanomolar potency. Specifically, compound 7b inhibits AChE with an IC50 1 nM and spares butyrylcholinesterase. Administration of 7b to mouse brain slices restores synaptic activity impaired by pirenzepine, a muscarinic M1-selective antagonist. Moreover, oral administration of 7b to C57BL/6 mice enhances hippocampal long-term potentiation in a dose-dependent manner and is detectable in the brain tissue. All these data supported that 7b is a potential cognitive enhancer and is worth for further exploration.
