Synthesis and molecular docking simulations of novel azepines based on quinazolinone moiety as prospective antimicrobial and antitumor hedgehog signaling inhibitors

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 12, 2024

A series of novel azepine derivatives based on quinazolinone moiety was synthesized through the reaction chalcones (2a-d) either with 2-amino aniline in acidic medium to give diazepines (3a-d) or 2-aminophenol offer oxazepine (4a-d). The structure compounds confirmed via melting points, elemental analyses, and different spectroscopic techniques. Moreover, these newly mode action investigated in-silico using molecular docking against outer membrane protein (OMPA), exo-1,3-beta-glucanase for their antimicrobial activity, Smoothened (SMO), transcription factor glioma-associated homology (SUFU/GLI-1), main proteins Hedgehog signaling pathway inspect anticancer potential. Our results showed that, diazepine (3a) (4a) offered highest binding energy target OMPA/ exhibited potent activities E. coli, P. aeruginosa, S. aureus, B. subtilis, C. Albicans A. flavus. As well, achieved best among other compounds, SMO, SUFU/GLI-1 proteins. in-vitro cytotoxic study done them panel cancer cell lines HCT-116, HepG2, MCF-7 normal line WI-38. Conclusively, it revealed that simulations experiments were agreed. a result, our findings elucidated (4a), have potential be used as agents possible treatment medications.

Язык: Английский

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Cinnamic acid conjugated with triazole acetamides as anti-Alzheimer and anti-melanogenesis candidates: an in vitro and in silico study

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 3, 2025

In this study, new cinnamic acid linked to triazole acetamide derivatives was synthesized and evaluated for anti-Alzheimer anti-melanogenesis activities. The structural elucidation of all analogs performed using different analytical techniques, including 1H-NMR, 13C-NMR, mass spectrometry, IR spectroscopy. compounds were assessed in vitro their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase enzymes. Among synthesize derivative compound 3-(4-((1-(2-((2,4-dichlorophenyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxyphenyl)acrylic (10j) exhibited the highest activity BChE with an IC50 value 11.99 ± 0.53 µM. Derivative 3-(3-methoxy-4-((1-(2-oxo-2-(p-tolylamino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)acrylic (10d), bearing a 4-CH3 group, identified as most potent AChE inhibitor. terms inhibition, 3-(3-methoxy-4-((1-(2-((2-methyl-4-nitrophenyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)acrylic (compound 10n), demonstrated 44.87% inhibition at concentration 40 Additionally, kinetic study 10j which 2,4-dichlorophenyl substituents revealed mixed-type pattern. Furthermore, molecular docking dynamic studies conducted thoroughly evaluate its mode action within active site.

Язык: Английский

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Anticholinesterase activities of novel isoindolin-1,3-dione-based acetohydrazide derivatives: design, synthesis, biological evaluation, molecular dynamic study

BMC Chemistry, Год журнала: 2024, Номер 18(1)

Опубликована: Апрель 1, 2024

Abstract In pursuit of developing novel cholinesterase (ChE) inhibitors through molecular hybridization theory, a series isoindolin-1,3-dione-based acetohydrazides (compounds 8a – h ) was designed, synthesized, and evaluated as possible acetylcholinesterase (AChE) butyrylcholinesterase (BChE) inhibitors. vitro results revealed IC 50 values ranging from 0.11 ± 0.05 to 0.86 0.02 µM against AChE 5.7 0.2 30.2 2.8 BChE. A kinetic study conducted on the most potent compound, , ascertain its mode inhibition, revealing competitive AChE. Furthermore, binding interaction modes active compound within site elucidated. Molecular dynamics simulations were performed assess stability -AChE complex. silico pharmacokinetic predictions for compounds indicated their potential promising lead structure development new anti-Alzheimer’s disease (anti-AD) agents.

Язык: Английский

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Synthesis, biological evaluation and molecular modeling studies of methyl indole-isoxazole carbohydrazide derivatives as multi-target anti-Alzheimer’s agents

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Сен. 10, 2024

Язык: Английский

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Highly efficient, catalyst-free, one-pot sequential four-component synthesis of novel spiroindolinone-pyrazole scaffolds as anti-Alzheimer agents: in silico study and biological screening

RSC Medicinal Chemistry, Год журнала: 2023, Номер 15(1), С. 207 - 222

Опубликована: Дек. 4, 2023

Alzheimer's disease is a neurodegenerative disorder that impacts memory, thinking, and behavior, currently, there no effective cure available for its treatment. This study explored one-pot strategy synthesizing spiroindolinone-pyrazole derivatives through sequential four-component condensation reaction. These were further investigated their potential as anti-Alzheimer's agents. The developed synthetic procedure provides remarkable advantages, including clean reaction profile, abundant starting materials, operational simplicity, easy purification without traditional methods with good to excellent yields (84-96%). Next, the biological potencies of newly synthesized against AChE BChE disease-related targets determined. Also, kinetic cytotoxicity most potent derivative investigated. Furthermore, molecular docking dynamics evaluations performed employing

Язык: Английский

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Amino-7,8-dihydro-4H-chromenone derivatives as potential inhibitors of acetylcholinesterase and butyrylcholinesterase for Alzheimer’s disease management; in vitro and in silico study

BMC Chemistry, Год журнала: 2024, Номер 18(1)

Опубликована: Апрель 10, 2024

In this article, we present the design and synthesis of amino-7,8-dihydro-4H-chromenone derivatives as possible inhibitors acetylcholinesterase (AChE) butyrylcholinesterase (BChE) for management Alzheimer's disease (AD). The target compounds were evaluated against AChE BChE in vitro, 4k exhibited good potency (IC

Язык: Английский

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Synthesis of novel aryl-substituted 2-aminopyridine derivatives by the cascade reaction of 1,1-enediamines with vinamidinium salts to develop novel anti-Alzheimer agents

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 14, 2024

Abstract Alzheimer’s disease (AD), a severe neurodegenerative disorder, imposes socioeconomic burdens and necessitates innovative therapeutic strategies. Current interventions are limited underscore the need for novel inhibitors of acetylcholinesterase (AChE) butyrylcholinesterase (BChE), enzymes implicated in pathogenesis AD. In this study, we report synthetic strategy generation 2-aminopyridine derivatives via two-component reaction converging aryl vinamidinium salts with 1,1-enediamines (EDAMs) dimethyl sulfoxide (DMSO) solvent system, catalyzed by triethylamine (Et 3 N). The protocol introduces rapid, efficient, scalable pathway, achieving good to excellent yields while maintaining simplistic workup procedures. Seventeen were synthesized subsequently screened their inhibitory activity against AChE BChE. most potent derivative, 3m , exhibited an IC 50 value 34.81 ± 3.71 µM 20.66 1.01 BChE compared positive control donepezil 0.079 0.05 10.6 2.1 Also, detailed kinetic studies undertaken elucidate modes enzymatic inhibition compounds both promising compound was then subjected molecular docking dynamics simulations, revealing significant binding affinities favorable interaction profiles silico ADMET assessments further determined drug-like properties suggesting it as candidate pre-clinical development.

Язык: Английский

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Synthesis of novel hybrids of 1,2,3-triazoles-hydrazone: targeting cholinesterases and Alzheimer's related genes

Future Medicinal Chemistry, Год журнала: 2024, Номер 16(15), С. 1519 - 1535

Опубликована: Июнь 12, 2024

Aim: A new series of 1,2,3-triazole-hydrazone derivatives were developed to evaluate their anti-Alzheimer's activity. Materials & methods: All compounds screened toward cholinesterases via the modified Ellman's method. The toxicity assay on SH-SY5Y cells was performed using MTT assay, and expression levels GSK-3α, GSK-3β, DYRK1 CDK5 assessed in presence 6m 6p. Results: 6p; acting as mixed-type inhibitors, exhibited promising acetylcholinesterase butyrylcholinesterase inhibitory activity, respectively. demonstrated no under tested concentrations positively impacted neurodegenerative pathways. Notably, displayed a significant downregulation mRNA GSK-3β CDK5. Conclusion: target could be considered developing disease agents.

Язык: Английский

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Chemoinformatics Study of Benzodiazepine-1, 2, 3-triazole Derivatives Targeting Butyrylcholinesterase

Journal of Fluorescence, Год журнала: 2024, Номер unknown

Опубликована: Июнь 17, 2024

Язык: Английский

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Photocatalyst‐Free Wavelength‐Dependant Sequential Ring Transformations of Pyrazolo[1,2‐a]pyrazolones

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(21), С. 4441 - 4451

Опубликована: Авг. 27, 2024

Abstract We report sequential wavelength‐selective photochemical transformations of 1‐alkenylpyrazolo[1,2‐ a ]pyrazolones to pyrazolo[1,2‐ ][1,2]diazepines or cyclobuta[ c ]pyrazolo[1,2‐ ]pyrazolones. Irradiation with visible‐light (blue LED, 457 nm) induced selective ‘ring switching’ transformation into ][1,2]diazepines, which underwent electrocyclisation yielding upon irradiation UV−A light (black 365 nm). Due the very narrow wavelength now available from OLED sources, formation either 5,7‐bicyclic 5,5,4‐tricyclic ring systems 5,5‐bicyclic starting material is possible by changing source. The took place under mild conditions in absence additives photocatalysts. Mechanistic studies indicate that these proceed through an excited triplet state substrate, followed homolytic C(1)−N(8) bond cleavage, intersystem crossing, and cyclization zwitterionic intermediate on ground potential energy surface. subsequent photoinduced disrotatory stereospecific 4π‐electrocyclization leads 3D‐rich products.

Язык: Английский

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