Novel biphenyl bis -sulfonamides as acetyl and butyrylcholinesterase inhibitors: Synthesis, biological evaluation and molecular modeling studies

Mutahir, Sadaf; Jończyk, Jakub; Bajda, Marek; Khan, Islam Ullah; Khan, Muhammad Asim; Ullah, Nisar; Ashraf, Muhammad; Quratulain, -; Riaz, Sadaf; Hussain, Sajjad; Yar, Muhammad

doi:10.1016/j.bioorg.2015.11.002

Cited by 61 publications

(26 citation statements)

References 26 publications

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“…In recent years, the new acetylcholinesterase inhibitors (AChEIs) have attracted many researchers. [15,16] Xanthones, widely exist in Polygalaceae, Guttiferae, Gentianaceae and some families of fungi and lichens, are well-known natural compounds. [17,18] They display a wide range of biological activities, such as antiinflammatory, [19] antitumor, [20] antioxidant [21] and inhibition of cholinesterase, [22] which has led to the xanthones being designated as 'privileged structures'.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

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Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC 50 = 2.403 � 0.002 μM for AChE and IC 50 = 31.221 � 0.002 μM for BuChE), and it was also a good antioxidant (IC 50 = 2.662 � 0.003 μM). Enzyme kinetic studies showed that this compound was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, its copper complex showed more significant inhibitory activity for AChE (IC 50 = 0.934 � 0.002 μM) and antioxidant activity (IC 50 = 1.064 � 0.003 μM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood-brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

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“…Nitrogen heterocyclic moieties such as pyrazoles and pyrimidines containing derivatives gained considerable attention in medicinal chemistry for their broad-spectrum pharmacological activities such as antimicrobial, anti-inflammatory, analgesic, enzyme inhibition, antioxidant, and anticancer. These moieties have leading position in drug designing as important pharmacophore [10][11][12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Screening of curcumin‐derived isoxazole, pyrazoles, and pyrimidines for their anti‐inflammatory, antinociceptive, and cyclooxygenase‐2 inhibition

et al. 2017

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Curcumin has shown pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its numerous derivatives for diverse and improved therapeutic roles. In this study, we have synthesized curcumin derivatives containing isoxazole, pyrazoles, and pyrimidines and then the synthesized molecules were evaluated for their anti-inflammatory and antinociceptive activities in experimental animal models. Acute toxicity of synthesized molecules was evaluated in albino mice by oral administration. Any behavioral and neurological changes were observed at dose of 10 mg/kg body weight.Additionally, cyclooxygenase-2 (COX-2) enzyme inhibition studies were performed through in vitro assays. In vivo anti-inflammatory studies showed that curcumin with pyrimidines was the most potent anti-inflammatory agent which inhibited induced edema from 74.7% to 75.9%. Compounds 7, 9, and 12 exhibited relatively higher prevention of writhing episodes than any other compound with antinociceptive activity of 73.2%, 74.9%, and 71.8%, respectively. This was better than diclofenac sodium (reference drug, 67.1% inhibition). Similarly, COX-2 in vitro inhibition assays results revealed that compound 12 (75.3% inhibition) was the most potent compound.Molecular docking studies of 10, 11, and 12 compounds in human COX-2 binding site revealed the similar binding modes as that of other COX-2-selective inhibitors. K E Y W O R D Santi-inflammatory, COX-2 inhibition, curcumin derivatives, molecular modeling Chemically curcumin is diferuloylmethane which has attracted much attention of medicinal chemists for various diseases and therapeutic agents development. It has shown its pharmacological safety and wide range of biological activities such as antibacterial to anticancer agent [1][2][3][4] . Currently, curcumin is acclaimed to be one of the most widely researched naturally occurring chemopreventive agent which is cytoprotective to healthy human cells [5][6][7] . In spite of important therapeutic application, limited therapeutic utility concerns are associated with curcumin because of its poor absorption and fast metabolism under physiological conditions [8] . Active methylene and keto moiety are believed to be responsible for its rapid metabolism. In order to circumvent the problem of rapid metabolism and to improve its pharmacokinetics profile, several synthetic modifications have been studied on carbonyl and active methylene moiety [9] . In present study, isoxazole, N-substituted pyrazoles, and pyrimidine ring were incorporated in this focused segment of curcumin. Nitrogen heterocyclic moieties such as pyrazoles and pyrimidines containing derivatives gained considerable attention in medicinal chemistry for

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“…Biphenyl moiety also served as central building block for basic liquid crystal [ 2 ] and fluorescent layers in OLEDs [ 3 ]. As for pharmaceutical uses, to date, there are two simple biphenyl derivatives which have been applied in clinical usage to treat hypertension [ 4 ] and inflammatory [ 5 ]; and many more are in development as potential anti-cholinesterase [ 6 ], anti-diabetic [ 7 ], anti-tumor [ 8 ], anti-cancer [ 9 ] and anti-leukemia agent [ 10 ], and as a potential therapeutics for cardiovascular disease [ 11 ] and osteoporosis [ 12 ]. The anti-tyrosinase activities of biphenyl-based compounds were also reported [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Novel biphenyl ester derivatives as tyrosinase inhibitors: Synthesis, crystallographic, spectral analysis and molecular docking studies

et al. 2017

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Biphenyl-based compounds are clinically important for the treatments of hypertension and inflammatory, while many more are under development for pharmaceutical uses. In the present study, a series of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl benzoates, 2(a-q), and 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl pyridinecarboxylate, 2(r-s) were synthesized by reacting 1-([1,1'-biphenyl]-4-yl)-2-bromoethan-1-one with various carboxylic acids using potassium carbonate in dimethylformamide at ambient temperature. Single-crystal X-ray diffraction studies revealed a more closely packed crystal structure can be produced by introduction of biphenyl moiety. Five of the compounds among the reported series exhibited significant anti-tyrosinase activities, in which 2p, 2r and 2s displayed good inhibitions which are comparable to standard inhibitor kojic acid at concentrations of 100 and 250 μg/mL. The inhibitory effects of these active compounds were further confirmed by computational molecular docking studies and the results revealed the primary binding site is active-site entrance instead of inner copper binding site which acted as the secondary binding site.

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Novel biphenyl bis -sulfonamides as acetyl and butyrylcholinesterase inhibitors: Synthesis, biological evaluation and molecular modeling studies

Cited by 61 publications

References 26 publications

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Screening of curcumin‐derived isoxazole, pyrazoles, and pyrimidines for their anti‐inflammatory, antinociceptive, and cyclooxygenase‐2 inhibition

Novel biphenyl ester derivatives as tyrosinase inhibitors: Synthesis, crystallographic, spectral analysis and molecular docking studies

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