Novel bis-ureido-substituted sulfaguanidines and sulfisoxazoles as carbonic anhydrase and acetylcholinesterase inhibitors

Molecular Diversity, Journal Year: 2022, Volume and Issue: 27(4), P. 1735 - 1749

Published: Sept. 22, 2022

Language: Английский

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Isolation of Some Phenolic Compounds from Plantago subulata L. and Determination of Their Antidiabetic, Anticholinesterase, Antiepileptic and Antioxidant Activity

Chemistry & Biodiversity, Journal Year: 2022, Volume and Issue: 19(8)

Published: July 7, 2022

Abstract In the current study, some phenolic compounds, including acteoside, isoacteoside, echinacoside, and arenarioside purified characterized from Plantago subulata . These compounds were tested for its antioxidant potential, Fe 3+ Cu 2+ reductive ability chelating effects. The inhibitory effects of isolated towards human carbonic anhydrase I II isoenzymes (hCA hCA II), butyrylcholinesterase (BChE) acetylcholinesterase (AChE), aldose reductase (AR) α‐glycosidase (α‐gly). K i values found these in range 0.24±0.05–1.38±0.34 μM against I, 0.194±0.018–1.03±0.06 II, 0.043±0.01–0.154±0.02 AChE, 3.92±1.08–11.93±4.45 BChE, 0.082±0.0008–1.68±0.42 AR, 6.93±2.74–17.17±6.70 α‐glycosidase. As a result, displayed inhibition studied all metabolic enzymes. They are promising candidates treating disorders like Alzheimer's disease, diabetes mellitus, glaucoma, leukemia, epilepsy.

Language: 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, Journal Year: 2022, Volume and Issue: 356(4)

Published: Dec. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 84(2), P. 275 - 295

Published: Jan. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 1280, P. 135077 - 135077

Published: Feb. 1, 2023

Language: Английский

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Astragalus Polysaccharide Ameliorates Renal Inflammatory Responses in a Diabetic Nephropathy by Suppressing the TLR4/NF-κB Pathway

Drug Design Development and Therapy, Journal Year: 2023, Volume and Issue: Volume 17, P. 2107 - 2118

Published: July 1, 2023

Diabetic nephropathy (DN), as a chronic inflammatory complication of diabetes, is characterized by hyperglycemia, albuminuria and edema, which ultimately becomes the leading cause end-stage renal disease (ESRD). Astragalus polysaccharide (APS), extracted from membranaceus, was widely used in treatment diabetes mellitus. However, functional roles APS ameliorate responses DN, remain poorly understood. Therefore, purpose this study to explore molecular mechanism on DN vivo vitro models. We explored beneficial effects streptozotocin (STZ)-induced rat model high glucose (HG)-treated glomerular podocyte model. The fasting blood (FBG) ratio kidney weight body were measured after 4 weeks treatment. injury parameters containing serum creatinine (Scr), urea nitrogen (BUN) 24 h urinary protein evaluated. pathological examination observed hematoxylin-eosin (HE) staining. levels IL-1β, IL-6 MCP-1 evaluated ELISA assay. proliferation podocytes determined using CCK-8 assay flow cytometry. qRT-PCR Western blot analysis performed determine amounts TLR4/NF-κB-related gene expression. Our results indicated that effectively decreased FBG, BUN, Scr damage when compared with STZ-induced group. Additionally, significantly ameliorated reducing cytokines IL-6, expression inhibiting TLR4/NF-κB pathway activity rats. Consistent vitro, HG-induced response also alleviated through administration. found injury, mechanisms perhaps related relieving attenuating signaling pathway.

Language: Английский

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Identification of a new class of potent aldose reductase inhibitors: Design, microwave-assisted synthesis, in vitro and in silico evaluation of 2-pyrazolines

Chemico-Biological Interactions, Journal Year: 2021, Volume and Issue: 345, P. 109576 - 109576

Published: July 9, 2021

Language: Английский

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Synthesis, biological evaluation, and in silico study of novel library sulfonates containing quinazolin‐4(3H)‐one derivatives as potential aldose reductase inhibitors

Drug Development Research, Journal Year: 2021, Volume and Issue: unknown

Published: Sept. 28, 2021

A series of novel sulfonates containing quinazolin-4(3H)-one ring derivatives was designed to inhibit aldose reductase (ALR2, EC 1.1.1.21). Novel quinazolinone (1-21) were synthesized from the reaction sulfonated aldehydes with 3-amino-2-alkylquinazolin-4(3H)-ones in glacial acetic acid good yields (85%-94%). The structures molecules characterized using IR, 1 H-NMR, 13 C-NMR, and HRMS. All quinazolinones demonstrated nanomolar levels inhibitory activity against ALR2 (KI s are range 101.50-2066.00 nM). Besides, 4-[(2-isopropyl-4-oxoquinazolin-3[4H]-ylimino)methyl]phenyl benzenesulfonate (15) showed higher inhibitor inhibited up 7.7-fold compared epalrestat, a standard inhibitor. Binding interactions between have been investigated Schrödinger Small-Molecule Drug Discovery Suite 2021-1, reported possible inhibitor-ALR2 interactions. Both vitro silico study results suggest that these require further molecular modification improve their drug nominee potency as an

Language: Английский

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Infection Medications: Assessment In‐Vitro Glutathione S‐Transferase Inhibition and Molecular Docking Study

ChemistrySelect, Journal Year: 2021, Volume and Issue: 6(43), P. 11915 - 11924

Published: Nov. 16, 2021

Abstract Glutathione S‐transferases (EC 2.5.1.18, GSTs), consisting of at least seven subfamilies, such as alpha, kappa, mu, pi, theta, zeta, and omega, are the family cytosolic proteins with many known functions also abundant in cells. Moreover, they play significant roles influencing efficacy bioavailability pharmaceutical agents humans. It is that multiple types cancer tissue frequently have high levels GSTs compared to corresponding healthy tissue. Herein, firstly, GST was purified from human erythrocytes by rapid straightforward chromatographic techniques. Subsequently, active infection medications, antimycotics (amphotericin B, anidulafungin, caspofungin), antibacterials (daptomycin, ertapenem, tigecycline), antiviral (ganciclovir) were assessed for their inhibitory actions versus GST. All drugs demonstrated micromolar potent activity towards Antifungal had K I constants ranging between 20.60±0.05 μM 50.43±0.12 μM, whilst antibacterial exhibited KIs range 20.92±0.09–114.80±0.41 μM. Daptomycin ertapenem competitive inhibition, while other noncompetitive inhibition. amphotericin B most ( =20.60±0.05 μM), contrast, drug ganciclovir highest inhibition constant =463.10±1.28 μM). Studying both in‐vitro molecular docking interactions silico activities these medications complex GST, an enzyme biologically important, demonstrates caused associations detected. The results here might provide structural guidance design more inhibitors.

Language: Английский

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N‐substituted phthalazine sulfonamide derivatives as non‐classical aldose reductase inhibitors

Journal of Molecular Recognition, Journal Year: 2022, Volume and Issue: 35(12)

Published: Sept. 8, 2022

Aldose reductase (AR, AKR1B1; EC 1.1.1.21) is an aldo-keto that has been widely investigated as enzyme crucially involved in the pathogenesis of several chronic complications, including nephropathy, neuropathy, retinopathy, and cataracts associated with diabetes mellitus. Although sulfonamides have reported to possess many other biological activities, continuation our interest designing discovering potent inhibitors AR, herein, we evaluated AR inhibitory potential N-substituted phthalazine sulfonamide derivatives 5a-l. The studies revealed all show excellent activity against KI constants ranging from 67.73 495.20 nM. Among these agents, 4-(6-nitro-1,4-dioxo-1,2,3,4-tetrahydrophthalazine-2-carbonyl)benzenesulfonamide (5e) 1,4-dioxo-3-(4-sulfamoylbenzoyl)-1,2,3,4-tetrahydrophthalazine-6-carboxylic acid (5f) showed prominent values 148.20 nM, respectively, vs were found be more than epalrestat (KI = 852.50 nM), only inhibitor currently used therapy. Moreover, molecular docking also performed rationalize binding site interactions (5a-l) target AR. According ADME-Tox, predicts determined ARIs displaying suitable drug-like properties. identified this study may develop lead therapeutic agents inhibiting diabetic complications.

Language: Английский

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