Design, synthesis and evaluation of quinoline- O -carbamate derivatives as multifunctional agents for the treatment of Alzheimer’s disease

Abstract

A series of novel quinoline- O -carbamate derivatives was rationally designed for treating Alzheimer’s disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual ee AChE/eqBuChE inhibitor with IC 50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1β and NO. In addition, compound 3f presented significant neuroprotective effect on A β 25-35 -induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl 3 -induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.

Quinoline–sulfonamides as a multi-targeting neurotherapeutic for cognitive decline: in vitro, in silico studies and ADME evaluation of monoamine oxidases and cholinesterases inhibitors

“…were used to perform the assay as previously reported method. 26 Line Weaver-Burk graphs were used to analyze the inhibitory effect and determine the type of inhibition. All the tested compounds (a5, a12, a11, a6) showed competitive inhibition toward MAO-A, MAO-B, AChE and BChE respectively as displayed in Fig.…”

Synthesis of Novel Oxime and Benzofuran Chemical Frameworks Possessing Potent Anticholinesterase Activity: A SAR Study Related to Alzheimer Disease

“…39 and 40 in the file of supporting information. (23): Yield: 0.76 g (83 %); m.p: 142 °C; FT-IR υ(cm À 1 , ATR): υ(=NÀ H) 3362 stretching bands, υ(CÀ H) 3166-3006, aromatic CÀ H stretching bands, υ(CÀ H) 2950-2849 aliphatic CÀ H stretching bands, υ(C=O) 1758 C=O stretching bands. 1 H NMR (500 MHz, CDCl 3 ) δ 8.48, s, 1H; 7.83, d (J = 1.93 Hz), 1H; 7.73, s, 1H; 7.59, t (J = 2.00 Hz), 1H; 7.52, dd (J = 8.77, 1.95 Hz), 1H; 7.42, m, 2H; 7.29, t (J = 8.10 Hz), 1H; 7.13, ddd (J = 7.99, 2.08, 1.02 Hz), 1H; 1.49, s, 9H.…”

“…For instance, carbamates show anti-Alzheimer activity. [23] Ketoximes are also precious compounds possessing some biological properties such as antifungal activity. [24] In the light of all these chemical and biological informations mentioned above, in the present study, we succeeded to synthesize 19 novel compounds (5-23) bearing oxime and benzofuran skeletons, besides 4 known compounds (1-4) through the synthetic methods in our previous studies.…”

Therapy and diagnosis of Alzheimer's disease: from discrete metal complexes to metal–organic frameworks

“…One outstanding example is the effective use of quinoline derivatives like clioquinol and 8-hydroxyquinoline which have entered clinical trials for AD. 90,91…”