Discovery of novel benzenesulfonamides incorporating 1,2,3-triazole scaffold as carbonic anhydrase I, II, IX, and XII inhibitors

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 239, С. 124232 - 124232

Опубликована: Март 29, 2023

Язык: Английский

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Novel beta-lactam substituted benzenesulfonamides: in vitro enzyme inhibition, cytotoxic activity and in silico interactions

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 42(12), С. 6359 - 6377

Опубликована: Авг. 4, 2023

In this study, a library of twelve beta-lactam-substituted benzenesulfonamides (

Язык: Английский

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Novel spiroindoline derivatives targeting aldose reductase against diabetic complications: Bioactivity, cytotoxicity, and molecular modeling studies

Bioorganic Chemistry, Год журнала: 2024, Номер 145, С. 107221 - 107221

Опубликована: Фев. 19, 2024

Язык: Английский

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Bioactivity, cytotoxicity, and molecular modeling studies of novel sulfonamides as dual inhibitors of carbonic anhydrases and acetylcholinesterase

Journal of Molecular Liquids, Год журнала: 2024, Номер 410, С. 125558 - 125558

Опубликована: Июль 18, 2024

Язык: Английский

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Synthesis and biological studies of pyrimidine derivatives targeting metabolic enzymes

Archiv der Pharmazie, Год журнала: 2024, Номер 357(8)

Опубликована: Май 21, 2024

Abstract Novel synthesized pyrimidine derivatives were investigated against carbonic anhydrase isoenzymes I and II (hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α‐glycosidase, aldose reductase (AR) enzymes associated with some common diseases such as epilepsy, glaucoma, Alzheimer's disease, diabetes, neuropathy. When the results examined, novel found to have effective inhibition abilities toward metabolic enzymes. IC 50 values K i calculated for each derivative compared positive controls. The exhibited in range of 39.16 ± 7.70–144.62 26.98 nM hCA I, 18.21 3.66–136.35 21.48 II, which is different pathological physiological processes, 33.15 4.85–52.98 19.86 on AChE, 31.96 8.24–69.57 21.27 BChE. Also, determined 17.37 1.11–253.88 39.91 α‐glycosidase 648.82 53.74–1902.58 98.90 AR Within scope study, types evaluated.

Язык: Английский

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Dynamics of small molecule-enzyme interactions: Novel benzenesulfonamides as multi-target agents endowed with inhibitory effects against some metabolic enzymes

Archives of Biochemistry and Biophysics, Год журнала: 2024, Номер 759, С. 110099 - 110099

Опубликована: Июль 14, 2024

Язык: Английский

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Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif

Archiv der Pharmazie, Год журнала: 2022, Номер 356(4)

Опубликована: Дек. 27, 2022

New Schiff base-bearing thiosemicarbazones (1-13) were obtained from 4-hydroxy-3,5-dimethoxy benzaldehyde and various isocyanates. The structures of the synthesized molecules elucidated in detail. Density functional theory calculations also performed to determine spectroscopic properties compounds. Moreover, enzyme inhibition activities these compounds investigated. They showed highly potent effects on acetylcholinesterase (AChE) human carbonic anhydrases (hCAs) (KI values are range 51.11 ± 6.01 278.10 40.55 nM, 60.32 9.78 300.00 77.41 64.21 9.99 307.70 61.35 nM for AChE, hCA I, II, respectively). In addition, molecular docking studies performed, confirmed by binding affinities most derivatives.

Язык: Английский

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Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors

Drug Development Research, Год журнала: 2023, Номер 84(2), С. 275 - 295

Опубликована: Янв. 4, 2023

Abstract Aldose reductase (AR) is a crucial enzyme of the polyol pathway through which glucose metabolized under conditions hyperglycemia related to diabetes. A series novel acetic acid derivatives containing quinazolin‐4(3 H )‐one ring ( 1–22 ) was synthesized and tested for in vitro AR inhibitory effect. All target compounds exhibited nanomolar activity against enzyme, all displayed higher as compared reference drug epalrestat. Among them, Compound 19 , named 2‐(4‐[(2‐[(4‐methylpiperazin‐1‐yl)methyl]‐4‐oxoquinazolin‐3(4 )‐ylimino)methyl]phenoxy)acetic acid, strongest effect with K I value 61.20 ± 10.18 nM. Additionally, these were investigated L929, nontumoral fibroblast cells, MCF‐7, breast cancer cells using MTT assay. Compounds 16 showed lower toxicity normal L929 cells. The compounds’ absorption, distribution, metabolism, excretion properties also evaluated. Molecular docking simulations used look into possible binding mechanisms inhibitors AR.

Язык: Английский

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A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations

Journal of Molecular Structure, Год журнала: 2023, Номер 1280, С. 135077 - 135077

Опубликована: Фев. 1, 2023

Язык: Английский

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Carbonic anhydrase inhibition by antiviral drugs in vitro and in silico

Journal of Molecular Recognition, Год журнала: 2023, Номер 36(12)

Опубликована: Окт. 8, 2023

Abstract Enzyme inhibition is a commonly utilized method for controlling enzymatic activity in various physiologically relevant biological systems. Herein, the selected five active antiviral drugs, abacavir, emtricitabine, lamivudine, ribavirin, and ritonavir, were assayed as inhibitors of two human isoforms metalloenzyme carbonic anhydrase ( h CA, EC 4.2.1.1) involved physiological/pathological conditions. For this aim, vitro silico studies performed to gain insights into plausible binding interactions affinities drugs within CA I II isoforms' sites. The I, an isoform some pathological conditions such retinal or cerebral edema, was moderately inhibited by these at micromolar concentrations with K s spanning from 0.49 ± 0.05 3.51 0.37 μM compared reference drug acetazolamide (AAZ, 0.19 0.01 μM). Moreover, II, promising target glaucoma, epilepsy, altitude sickness, reasonably agents, range 0.64 0.08–5.80 AAZ 0.17 Both results demonstrated significant between CAs that they can support therapeutic targets against above‐mentioned Additionally, obtained will help optimize clinical dosage regimens avoid drug–drug unexpectedly when used combination other agents.

Язык: Английский

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