24416-78-2Relevant articles and documents
Design and synthesis of novel coumarin derivatives as potential acetylcholinesterase inhibitors for Alzheimer's disease
Amin, Kamilia M.,Abdel Rahman, Doaa E.,Abdelrasheed Allam, Heba,El-Zoheiry, Haidy H.
, (2021/05/04)
Twenty novel 7-benzyloxycoumarin based compounds were synthesized with a variety of bioactive chemical fragments. The synthesized compounds showed remarkable acetylcholinesterase (AChE) inhibitory activity. In vitro assay revealed that compounds 7-benzyloxy-4-{[(4-phenylthiazol-2(3H)-ylidene)hydrazono]methyl}-2H-chromen-2-one (5b, IC50= 0.451μM), 7-benzyloxy-4-({[4-(4-methoxyphenyl)thiazol-2(3H)-ylidene]hydrazono}methyl)-2H-chromen-2-one (5d, IC50= 0.625μM), 5-amino-1-[2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-1H-pyrazole-4-carbonitrile (13c, IC50= 0.466μM), 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)-N-(2-methylimino-4-phenylthiazol-3(2H)-yl)acetamide (16a, IC50= 0.500μM) and 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)-N-[4-(4-methoxyphenyl)-2-methyliminothiazol-3(2H)-yl]acetamide (16b, IC50= 0.590μM) exhibited promising AChE inhibitory activity even better than donepezil (IC50= 0.711μM). Kinetic study for compound 5b implied mixed type inhibitor which could bind peripheral anionic site (PAS) and catalytic active site (CAS) of AChE enzyme. In addition, in vivo evaluation of compounds 5b, 13c and 16a confirmed significant memory improvement in scopolamine-induced impairment model in tested mice. Furthermore, in silico studies were performed on the synthesized compounds which included molecular docking study at the active site of recombinant human acetylcholinesterase enzyme (rhAChE) as well as prediction of ADMET and other physicochemical parameters. A correlation between the docking results and IC50 of tested compounds was routinely observed and shared similar binding pattern to the co-crystallized ligand donepezil.
Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease
Joubert, Jacques,Foka, Germaine B.,Repsold, Benjamin P.,Oliver, Douglas W.,Kapp, Erika,Malan, Sarel F.
, p. 853 - 864 (2016/10/26)
A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1–25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1–8, 10–13) showing nano-molar hMAO-B inhibition (IC50: 0.5–73?nM). Limited ChE inhibitory activity was however observed for the benzyloxy series with the exception of 2 and especially 3 showing selective BuChE inhibition. From this series 3 showed the best multifunctional activity (eqBuChE IC50?=?0.96?μM, hMAO-A IC50?=?2.13?μM, hMAO-B IC50?=?0.0021?μM). Within the N-benzylpiperidine (16–19) and p-bromo-N-benzylpiperizine (21–24) series the compounds in general showed moderate ChE and MAO-B inhibitory activity. Of these compounds 19 was the most potent multifunctional agent showing good eeAChE and eqBuChE inhibition (IC50?=?9.10?μM and 5.90?μM, respectively), and relatively potent and selective hMAO-B inhibition (IC50?=?0.30?μM, SI?= >33). Molecular modeling revealed that 19 was able to bind simultaneously to the CAS, mid-gorge and PAS sites of AChE and BuChE suggesting that it will be able to inhibit AChE induced Aβ aggregation. From this study, compounds that 3 and 19 can be considered as promising multifunctional lead compounds.
4-Methylcoumarins with cytotoxic activity against T24 and RT4 human bladder cancer cell lines
Vianna,Ruschel,Dietrich,Figueiró,Morrone,Canto,Corvello,Velho,Crestani,Teixeira,Von Poser,Battastini,Eifler-Lima
, p. 905 - 911 (2015/05/27)
Bladder cancer is one of the most prevalent malignancies of the genitourinary tract, and approximately 25% of patients develop superficial cancers with invasive and metastatic pathology. Coumarins and their derivatives have antiproliferative activity and
