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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Acylhydrazones and Their Biological Activity: A Review

Molecules, Год журнала: 2022, Номер 27(24), С. 8719 - 8719

Опубликована: Дек. 9, 2022

Due to the structure of acylhydrazones both by pharmacophore –CO–NH–N= group and different substituents present in molecules compounds this class, various pharmacological activities were reported, including antitumor, antimicrobial, antiviral, antiparasitic, anti-inflammatory, immunomodulatory, antiedematous, antiglaucomatous, antidiabetic, antioxidant, actions on central nervous system cardiovascular system. This fragment is found several drugs used therapy some diseases that are at top public health problems, like microbial infections diseases. Moreover, acylhydrazone moiety with possible applications treatment other pathologies, such as schizophrenia, Parkinson’s disease, Alzheimer’s Huntington’s disease. Considering these aspects, we consider a study literature data regarding structural biological properties useful.

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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Design, synthesis, antioxidant and anticholinesterase activities of novel isonicotinic hydrazide-hydrazone derivatives

Journal of Molecular Structure, Год журнала: 2023, Номер 1279, С. 135037 - 135037

Опубликована: Янв. 27, 2023

Язык: Английский

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New naphthoquinone thiazole hybrids as carbonic anhydrase and cholinesterase inhibitors: Synthesis, crystal structure, molecular docking, and acid dissociation constant

Journal of Molecular Structure, Год журнала: 2023, Номер 1301, С. 137365 - 137365

Опубликована: Дек. 19, 2023

Язык: Английский

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Autophagy, Pyroptosis and Ferroptosis are Rising Stars in the Pathogenesis of Diabetic Nephropathy

Diabetes Metabolic Syndrome and Obesity, Год журнала: 2024, Номер Volume 17, С. 1289 - 1299

Опубликована: Март 1, 2024

Abstract: Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes and can potentially develop into end-stage renal disease. Its pathogenesis complex not fully understood. Podocytes, glomerular endothelial cells (GECs), mesangial (GMCs) tubular epithelial (TECs) play important roles normal function glomerulus tubules, their injury involved progression DN. Although our understanding mechanisms leading to DN has substantially improved, we still need find more effective therapeutic targets. Autophagy, pyroptosis ferroptosis are programmed cell death processes that associated with inflammation closely related a variety diseases. Recently, growing number studies have reported autophagy, regulate podocytes, GECs, GMCs TECs. This review highlights contributions pyroptosis, these cells, offering potential targets for treatment. Keywords: diabetic nephropathy, ferroptosis,

Язык: Английский

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Surface characterization of barium(II)‐selective potentiometric sensor based on a newly synthesized thiosemicarbazone derivative molecule

Electroanalysis, Год журнала: 2024, Номер 36(7)

Опубликована: Март 4, 2024

Abstract In this study, we synthesized a new thiosemicarbazone derivative molecule ( 5 ) that exhibits sensor properties. The characterization of the was performed using spectroscopic methods such as 1 H−, 13 C–NMR, FT–IR and Q–TOF. PVC‐membrane ion‐selective sensors were prepared in which used an ionophore. Surface images examined by scanning electron microscope (SEM) technique. exhibited selectivity towards barium(II) ions. developed barium(II)‐selective had low detection limit 5.54×10 −7 M concentration range 1.0×10 −1 –1.0×10 −6 M. proposed fast response time, good repeatability stability, can be manufactured with cost. detect ions various water samples very high recoveries.

Язык: Английский

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A series of quinazolin‐4(3H)‐one‐morpholine hybrids as anti‐lung‐cancer agents: Synthesis, molecular docking, molecular dynamics, ADME prediction and biological activity studies

Chemical Biology & Drug Design, Год журнала: 2024, Номер 104(1)

Опубликована: Июль 1, 2024

Abstract In this study, we synthesized 15 novel quinazoline‐morpholinobenzylideneamino hybrid compounds from methyl anthranilate and assessed their cytotoxicity via in vitro assays against A549 BEAS‐2B cell lines. Molecular docking studies were conducted to evaluate the protein‐ligand interactions inhibition mechanisms on nine different molecular targets, while dynamics (MD) simulations carried out assess stability of best docked ligand–protein complexes. Additionally, ADME prediction was determine physicochemical parameters drug likeness. According assays, compound 1 (IC 50 = 2.83 μM) found be most active inhibitor cells. While selectivity index (SI) is 29, SI reference drugs paclitaxel sorafenib, used are 2.40 4.92, respectively. Among compounds, has scores VEGFR1 (−11.744 kcal/mol), VEGFR2 (−12.407 kcal/mol) EGFR (−10.359 kcal/mol). During MD simulations, consistently exhibited strong hydrogen bond with sites 2, these maintained for more than 90% simulation time. RMSD RMSF values complexes high at minimum levels around 1–2 Å. conclusion, findings suggest that may a potent selective candidate lung cancer treatment VEGFR2, especially.

Язык: Английский

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