Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives

Alipour, Mohammad Amin; Khoobi, Mehdi; Moradi, Alireza; Nadri, Hamid; Moghadam, Farshad Homayouni; Emami, Saeed; Hasanpour, Zeinab; Foroumadi, Alireza; Shafiee, Abbas

doi:10.1016/j.ejmech.2014.05.056

Cited by 72 publications

(27 citation statements)

References 25 publications

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“…Among the various classes of compounds studied for design of new AChE inhibitors, coumarin scaffold has received great attention, due to its ability for binding to peripheral anionic site (PAS) of AChE [18]. Recently, we have reported different series of coumarinbased AChE inhibitors [19][20][21][22][23]. On the other hand, some authors have described the usefulness of indole amine framework in the design of new AChE inhibitors or multi-target agents for AD therapy.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety

Ghanei-Nasab

Khoobi

Hadizadeh

et al. 2016

European Journal of Medicinal Chemistry

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Section: Introductionmentioning

confidence: 99%

Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety

Ghanei-Nasab

Khoobi

Hadizadeh

et al. 2016

European Journal of Medicinal Chemistry

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“…The coumarin ring has been of high interest as a scaffold for design of several potent AChEIs . In previous studies, coumarin moiety showed affinity to the PAS of AChE due to its aromatic character that facilitates the π‐π interaction with the amino acid residues in the region.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2‐(2‐oxo‐2H‐chromen‐4‐yl)acetamides as potent acetylcholinesterase inhibitors and molecular insights into binding interactions

Kara

Suwanhom

Wattanapiromsakul

et al. 2019

Archiv der Pharmazie

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Sixteen novel coumarin-based compounds are reported as potent acetylcholinesterase (AChE) inhibitors. The most active compound in this series, 5a (IC 50 0.04 ± 0.01 µM), noncompetitively inhibited AChE with a higher potency than tacrine and galantamine.Compounds 5d, 5j, and 5 m showed a moderate antilipid peroxidation activity. The compounds showed cytotoxicity in the same range as the standard drugs in HEK-293 cells. Molecular docking demonstrated that 5a acted as a dual binding site inhibitor. The coumarin moiety occupied the peripheral anionic site and showed π-π interaction with Trp278. The tertiary amino group displayed significant cation-π interaction with Phe329.The aromatic group showed π-π interaction with Trp83 at the catalytic anionic site. The long chain of methylene lay along the gorge interacting with Phe330 via hydrophobic interaction. Molecular docking was applied to postulate the selectivity toward AChE of 5a in comparison with donepezil and tacrine. Structural insights into the selectivity of the coumarin derivatives toward huAChE were explored by molecular docking and 3D QSAR and molecular dynamics simulation for 20 ns. ADMET analysis suggested that the 2-(2oxo-2H-chromen-4-yl)acetamides showed a good pharmacokinetic profile and no hepatotoxicity. These coumarin derivatives showed high potential for further development as anti-Alzheimer agents. K E Y W O R D S 3D QSAR, acetylcholinesterase inhibitor, coumarin, lipid peroxidation, molecular docking 1 | INTRODUCTION Alzheimerʼs disease (AD) is the most common form of dementia. The symptoms start with difficulty in remembering new information and recent events, followed by apathy, depression, subsequent impaired judgment, confusion, and behavior change. Etiology of AD is complicated and still unclear. β-Amyloid aggregation and neurofibrillary tangles are major abnormalities found in the brain of patients with AD, which eventually lead to neuronal damage. This results in the decrease of acetylcholine (ACh), the neurotransmitter responsible for memory and learning. Acetylcholinesterase inhibitors (AChEIs), such as tacrine, donepezil, galantamine, and rivastigmine, Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Kara J, Suwanhom P, Wattanapiromsakul C, et al. Synthesis of 2-(2-oxo-2Hchromen-4-yl)acetamides as potent acetylcholinesterase inhibitors and molecular insights into binding interactions.

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“…Although these compounds exhibit multi-beneficial pharmacological properties, isolation and purification of umbelliferone and its derivatives from plants are problematic due to low concentration and seasonal and regional dependency [12]. On the other hand, chemical synthesis requires the usage of hazardous agents, long synthetic steps, and extreme reaction conditions [13, 14]. …”

Section: Introductionmentioning

confidence: 99%

Synthesis of umbelliferone derivatives in Escherichia coli and their biological activities

et al. 2017

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BackgroundUmbelliferone, also known as 7-hydroxycoumarin, is a phenolic metabolite found in many familiar plants. Its derivatives have been shown to have various pharmacological and chemo-preventive effects on human health. A uridine diphosphate glycosyltransferase YjiC from Bacillus licheniformis DSM 13, a cytochrome P450BM3 (CYP450 BM3) variant namely mutant 13 (M13) from Bacillus megaterium, and an O-methyltransferase from Streptomyces avermitilis (SaOMT2) were used for modifications of umbelliferone.ResultsThree umbelliferone derivatives (esculetin, skimmin, and herniarin) were generated through enzymatic and whole cell catalysis. To improve the efficiencies of biotransformation, different media, incubation time and concentration of substrate were optimized and the production was scaled up using a 3-L fermentor. The maximum yields of esculetin, skimmin, and herniarin were 337.10 μM (67.62%), 995.43 μM (99.54%), and 37.13 μM (37.13%), respectively. The water solubility of esculetin and skimmin were 1.28-folds and 3.98-folds as high as umbelliferone, respectively, whereas herniarin was 1.89-folds less soluble than umbelliferone. Moreover, the antibacterial and anticancer activities of herniarin showed higher than umbelliferone, esculetin and skimmin.ConclusionsThis study proves that both native and engineered enzymes could be employed for the production of precious compounds via whole cell biocatalysis. We successfully produced three molecules herniarin, esculetin and skimmin in practical amounts and their antibacterial and anticancer properties were accessed. One of the newly synthesized molecules the present research suggests that the combinatorial biosynthesis of different biosynthetic enzymes could rapidly promote to a novel secondary metabolite.Electronic supplementary materialThe online version of this article (doi:10.1186/s13036-017-0056-5) contains supplementary material, which is available to authorized users.

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Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives

Cited by 72 publications

References 25 publications

Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety

Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety

Synthesis of 2‐(2‐oxo‐2H‐chromen‐4‐yl)acetamides as potent acetylcholinesterase inhibitors and molecular insights into binding interactions

Synthesis of umbelliferone derivatives in Escherichia coli and their biological activities

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