In Vitro Inhibitory Activity and Molecular Docking Study of Selected Natural Phenolic Compounds as AR and SDH Inhibitors**

ChemistrySelect, Год журнала: 2022, Номер 7(48)

Опубликована: Дек. 20, 2022

Abstract Polyol pathway enzymes, aldose reductase (EC 1.1.1.21; AR, ALR2), and sorbitol dehydrogenase 1.1.1.14; SDH, SORD) have been widely investigated as the enzymes crucially involved in pathogenesis of several chronic complications, including nephropathy, neuropathy, retinopathy, cataracts associated with diabetes mellitus. Although phenolic compounds reported to possess many other biological activities, continuation our interest designing discovering potent inhibitors AR herein, we evaluated these agents’ inhibitory potential against polyol enzymes. Our vitro studies revealed that all derivatives show activity recombinant human (r h AR) SDH SDH), K I constants ranging from 9.37±0.16 μM 77.22±2.49 2.51±0.10 42.16±1.03 μM, respectively. Among agents, Prunetin Phloridzin showed prominent versus r while some were also determined perfect dual activity. Moreover, silico performed rationalize binding site interactions agents target enzyme SDH. According ADME‐Tox was be exhibiting suitable drug‐like properties. The identified therapeutic potentials this study may promising for developing lead prevent complications.

Язык: Английский

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A new series of hydrazones as small‐molecule aldose reductase inhibitors

Archiv der Pharmazie, Год журнала: 2023, Номер 356(4)

Опубликована: Янв. 5, 2023

In the search for small-molecule aldose reductase (AR) inhibitors, new tetrazole-hydrazone hybrids (1-15) were designed. An efficient procedure was employed synthesis of compounds 1-15. All hydrazones subjected to an in vitro assay assess their AR inhibitory profiles. Compounds 1-15 caused inhibition with Ki values ranging between 0.177 and 6.322 µM IC50 0.210 0.676 µM. 2-[(1-(4-Hydroxyphenyl)-1H-tetrazol-5-yl)thio]-N'-(4-fluorobenzylidene)acetohydrazide (4) most potent inhibitor this series. Compound 4 markedly inhibited (IC50 = 0.297 µM) a competitive manner (Ki compared epalrestat 0.857 µM, 0.267 µM). Based on data obtained by applying MTT test, compound showed no cytotoxic activity toward normal (NIH/3T3) cells at tested concentrations, indicating its safety as inhibitor. exhibited proper interactions crucial amino acid residues within active site AR. silico QikProp all also determined pharmacokinetic Taken together, stands out promising further vivo studies.

Язык: Английский

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The anti-Alzheimer potential of novel spiroindolin-1,2-diazepine derivatives as targeted cholinesterase inhibitors with modified substituents

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Июль 24, 2023

Abstract In this study, a new series of spiro indolin-1,2-diazepine were designed, synthesized, and screened for their cholinesterase inhibitory activities. A novel, green, high-yielding approach was constructed to synthesize derivatives through cascade reaction different isatins, malononitrile 1,1-enediamines (EDAMs) via sequential four-component reactions produce the target compounds with good excellent yields. Next potencies all determined spectroscopically at 415 nm using modified Ellman method. The results in vitro screening indicated that 5l spiroindolin-1,2-diazepine core bearing 5-NO 2 R 1 4-OH most potent selective AChE inhibitor an IC 50 value 3.98 ± 1.07 µM no significant inhibition against BChE while 5j active analog both enzymes. structure–activity relationships suggested variation activities affected by substitutions on indolinone ring as well phenyl moiety. enzyme kinetic studies compound five concentrations acetylthiocholine substrate (0.1–1 mM) Ellman's method revealed it inhibited mixed mode K i 0.044 μM. molecular docking study performed induced fit protocol predict putative binding interaction. It shown moieties used initial structure design play fundamental role interacting enzyme's site. Further, dynamics simulations Schrödinger package complex formed stable enzyme. MTT toxicity assessments neuroblastoma cell line executed, seen under tested concentrations.

Язык: Английский

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New N -(1,3,4-thiadiazole-2-yl)acetamide derivatives as human carbonic anhydrase I and II and acetylcholinesterase inhibitors

Journal of Biomolecular Structure and Dynamics, Год журнала: 2024, Номер unknown, С. 1 - 19

Опубликована: Март 27, 2024

Various carbonic anhydrase (CA) enzyme isoforms are known today. In addition to the use of CA inhibitors as diuretics, antiepileptics and antiglaucoma agents, inhibition other specific was reported have clinical benefits in cancers. this study, two groups 1,3,4-thiadiazole derivatives were designed synthesized act human I II (hCA hCA II) inhibitors. The activities these compounds tested vitro evaluated silico studies. activity also against acetylcholinesterase (AChE) evaluate relation newly structures AChE. analyzed by 1H NMR,13C NMR high-resolution mass spectroscopy (HRMS). results displayed a better all than that commonly used standard drug, Acetazolamide (AAZ). showed II, except for 5b 6b. Only 6a 6c superior AChE compared agent, tacrine (THA). studies, including absorption, distribution, metabolism excretion (ADME) drug-likeness evaluation, molecular docking, dynamic simulations (MDSs) density functional theory (DFT) calculations, compatible with presented details regarding structure–activity relationship.

Язык: Английский

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Novel composite structures based on cobalt phthalocyanine/graphene oxide: Identification of potential drug candidates to treat Alzheimer’s disease and diabetes

Inorganica Chimica Acta, Год журнала: 2024, Номер 570, С. 122190 - 122190

Опубликована: Июнь 6, 2024

Язык: Английский

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