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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Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

ChemistrySelect, Год журнала: 2023, Номер 8(25)

Опубликована: Июль 3, 2023

Abstract In this study, imines bearing quinazolin‐4(3 H )‐one were synthesized and their inhibitory properties investigated against some metabolic enzymes including Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), α‐Glycosidase (α‐Gly), human Carbonic Anhydrase I–II (hCA I–II). All compounds had strength with K i values in the range of 38.55±4.08–159.05±10.68 nM 41.04±6.73–177.12±8.06 hCA I hCA‐II, respectively comparison to standard acetazolamide (AZA) =125.15±0.78 (for hCA‐I) =148.75±0.92 hCA‐II). The showed potent activity α ‐Gly enzyme IC 50 value 0.34–2.28 (standard inhibitor acarbose (ACR): 3.18 nM). Also, these analogs 4.20±0.15–26.10±2.36 AChE 1.22±0.05–16.09±0.88 BChE tacrine (TAC) =37.62±6.86 AChE) =26.75±5.79 BChE). Additionally, molecular docking dynamics simulation study was carried out for determination ligand‐enzyme interactions. scores most active compound calculated as −7.31, −7.59, −6.66, −6.93 −7.11 kcal/mol AChE, BChE, I, II, α‐Gly, respectively.

Язык: Английский

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Novel quinazoline–chromene hybrids as anticancer agents: Synthesis, biological activity, molecular docking, dynamics and ADME studies

Archiv der Pharmazie, Год журнала: 2023, Номер 356(11)

Опубликована: Сен. 21, 2023

In this study, new quinazoline-chromene hybrid compounds were synthesized. The cytotoxic effects on cell viability of the tested against A549 human lung adenocarcinoma and BEAS-2B healthy bronchial epithelial lines in vitro. addition, ability active to inhibit migration was tested. Molecular docking studies performed evaluate ligand-protein interactions, molecular dynamics simulations determine interactions stability complexes. silico absorption, distribution, metabolism, excretion (ADME) conducted estimate drug-likeness compounds. Compounds 4 (IC50 = 51.2 µM) 5 44.2 found be most agents cells. They are more selective cells than reference drug doxorubicin. also have significantly migration. best scores epidermal growth factor receptor (EGFR) (-11.300 -11.226 kcal/mol) vascular endothelial 2 (VEGFR2) (-10.987 -11.247 kcal/mol), respectively. MD simulations, strong hydrogen bond above 80% simulation times showed a low ligand root mean square deviation (RMSD) around Å. According ADME analysis, exhibit excellent pharmacokinetic characteristics.

Язык: Английский

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New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

Chemistry & Biodiversity, Год журнала: 2023, Номер 20(8)

Опубликована: Июнь 29, 2023

In this study, twenty new anthranilic acid hydrazones 6-9 (a-e) were synthesized and their structures characterized by Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (1 H-NMR - 13 C-NMR), High-resolution Mass Spectroscopy (HR-MS). The inhibitory effects of the compounds against COX-II evaluated. IC50 values found in range >200-0.32 μM 6e, 8d, 8e, 9b, 9c, 9e determined to be most effective inhibitors. Cytotoxic potent investigated human hepatoblastoma (Hep-G2) healthy embryonic kidney (Hek-293) cell lines. Doxorubicin (IC50 : 8.68±0.16 for Hep-G2, 55.29±0.56 Hek-293) was used as standard. 8e is active compound, with low Hep-G2 (4.80±0.04 μM), high Hek-293 (159.30±3.12), selectivity (33.15). Finally, molecular docking dynamics studies performed understand ligand-protein interactions between COX II, Epidermal Growth Factor Receptor (EGFR), Transforming beta II (TGF-βII). scores calculated -10.609--6.705 kcal/mol COX-II, -8.652--7.743 EGFR, -10.708--8.596 TGF-βII.

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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Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma, Alzheimer's Disease and Diabetes Mellitus

Chemistry & Biodiversity, Год журнала: 2023, Номер 20(10)

Опубликована: Сен. 11, 2023

Quinazolinones, which represent an important part of nitrogen-containing six-membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from reaction acylated derivatives 4-hydroxy benzaldehyde with 3-amino-2-alkylquinazolin-4(3H)-ones good yields (85-94 %) and structures characterized using Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (1 H-NMR, 13 C-NMR), High-Resolution Mass Spectroscopy (HR-MS). As application inhibition properties compounds on α-Glucosidase (α-Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), Carbonic anhydrase I-II (hCA I-II) metabolic enzymes investigated. All showed at nanomolar level Ki values range 12.73±1.26-93.42±9.44 nM for AChE, 8.48±0.92-25.84±2.59 BChE, 66.17±5.16-818.06±44.41 α-Glu, 2.56±0.26-88.23±9.72 hCA I, 1.68±0.14-85.43±7.41 II. Molecular docking study was performed understand interactions most potent corresponding enzymes. Also, absorption, distribution, metabolism, excretion, toxicity (ADME/T)

Язык: Английский

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Aldose reductase with quinolone antibiotics interaction: In vitro and in silico approach of its relationship with diabetic complications

Archives of Biochemistry and Biophysics, Год журнала: 2024, Номер unknown, С. 110161 - 110161

Опубликована: Сен. 1, 2024

Язык: Английский

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The Role of Immune Cells in DKD: Mechanisms and Targeted Therapies

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 2103 - 2118

Опубликована: Апрель 1, 2024

Diabetic kidney disease (DKD), is a common microvascular complication and major cause of death in patients with diabetes.Disorders immune cells cytokines can accelerate DKD development number ways.As the composed complex highly differentiated cells, interactions among different cell types play important regulatory roles development.Here, we summarize latest research into molecular mechanisms underlying various renal DKD.In addition, discuss most recent studies related to single technology bioinformatics analysis field DKD.The aims our review were explore as potential therapeutic targets provide some guidance for future clinical treatments.

Язык: Английский

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