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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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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Effects of Carnosic and Usnic Acid on Pentose Phosphate Pathway Enzymes: An Experimental and Molecular Docking Study

ChemistrySelect, Год журнала: 2024, Номер 9(27)

Опубликована: Июль 12, 2024

Abstract 6‐phosphogluconate dehydrogenase (6PGD) and Glucose‐6‐phosphate (G6PD) are crucial enzymes involved in generating cellular reducing power. Modifying the balance of reduced NADPH is considered essential for cancer advancement combined therapeutic strategies. Usnic acid (UA) a physiologically active dibenzofuran derivative. Carnosic (CA) phenolic diterpene that has been isolated from several plants. This work evaluated inhibitory effects UA CA on G6PD 6PGD by vitro tests. Molecular docking studies were employed to predict mechanisms inhibition. IC 50 values determined be 49.50 μM 77.00 G6PD, 69.30 57.75 6PGD, respectively. The K i 35.01±7.69 43.46±10.48 104.87±11.86 31.17±2.55 was identified as most effective inhibitor against whereas exhibited best activity with estimated binding energies −8.0 −7.8 kcal/mol, respectively, molecular studies. Ultimately, it shown results obtained silico methods study strongly associated. These chemicals′ structure might assist creating medications focus pentose phosphate pathway.

Язык: Английский

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Exploration of Some Bis‐Sulfide and Bis‐Sulfone Derivatives as Non‐Classical Aldose Reductase İnhibitors

ChemistrySelect, Год журнала: 2023, Номер 8(5)

Опубликована: Фев. 2, 2023

Abstract Aldose reductase (AR, ALR2; EC 1.1.1.21), an enzyme that converts glucose to fructose on the polyol pathway, is important member of Aldo‐keto superfamily. ALR2 part rate‐limiting step, which associated with diabetic complications in this process, and plays a role regulating reactive oxygen species induced by growth factors cytokines. Despite fact sulfides sulfones have been discovered variety other biological functions, current study, we assessed inhibitory potential derivatives bis‐sulfide ( 5 – i ) bis‐sulfone 6 order further our interest designing discovering powerful inhibitors. The results investigations showed all exhibit activity against ALR2, K I values ranging from 0.53±0.03 4.20±0.06 μM. Among these agents, 2,6‐bis((4‐chlorophenyl)(phenylthio)methyl)cyclohexan‐1‐one h ), 2,6‐bis((3‐nitrophenyl)(phenylthio)methyl)cyclohexan‐1‐one c 2,6‐bis((3‐chlorophenyl)(phenylthio)methyl)cyclohexan‐1‐one g exhibited prominent constants μM, 0.65±0.04 0.71±0.05 respectively, were found be more potent than epalrestat =0.79±0.01 μM) currently, only inhibitor (ALR2I) utilized treatment. Additionally, silico molecular docking experiments carried out explain how bis‐sulfides bis‐sulfones interacted target ALR2′s binding site. According ADME‐Tox compounds are predicted ALR2Is appropriate drug‐like characteristics. study‘s findings could exploited create innovative therapeutics prevent diabetes complications.

Язык: Английский

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Potential Implications of Hyperoside on Oxidative Stress-Induced Human Diseases: A Comprehensive Review

Journal of Inflammation Research, Год журнала: 2023, Номер Volume 16, С. 4503 - 4526

Опубликована: Окт. 1, 2023

Abstract: Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus , also detected many plant species such as Abelmoschus manihot Ribes nigrum Rosa rugosa Agrostis stolonifera Apocynum venetum Nelumbo nucifera . This compound exhibits multitude biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects neuroprotective effects, etc. review summarizes quantification, original plant, chemical structure property, structure–activity relationship, pharmacologic effect, pharmacokinetics, toxicity clinical application hyperoside, which will be significant for exploitation new drug full utilization this compound. Keywords: structure, pharmacology,

Язык: Английский

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Protective effect of bromelain on some metabolic enzyme activities in tyloxapol‐induced hyperlipidemic rats

Biotechnology and Applied Biochemistry, Год журнала: 2023, Номер 71(1), С. 17 - 27

Опубликована: Сен. 25, 2023

Abstract Elevation of one or more plasma lipids, such as phospholipids, cholesterol esters, cholesterol, and triglycerides, is known hyperlipidemia. In humans experimental animals, bromelain, the primary active ingredient isolated from pineapple stems, has several positive effects, including anti‐tumor growth, anticoagulation, anti‐inflammation. Hence, purpose this study was to determine possible protective impact bromelain on some metabolic enzymes (paraoxonase‐1, glutathione S ‐transferase, reductase, sorbitol dehydrogenase [SDH], aldose reductase [AR], butyrylcholinesterase [BChE], acetylcholinesterase [AChE]), activity in heart, kidney, liver rats with tyloxapol‐induced Rats were divided into three groups: control group, HL‐control group (tyloxapol 400 mg/kg, i.p. administered group), HL+bromelain (group receiving 250 mg/kg/o.d. prior administration tyloxapol i.p.). BChE, SDH, AR enzyme activities significantly increased all tissues compared control, whereas other studied decreased. Bromelain had a regulatory effect activities. conclusion, these results prove that new mediator decreases

Язык: Английский

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Recent Advances in Xanthine Oxidase Inhibitors

Mini-Reviews in Medicinal Chemistry, Год журнала: 2023, Номер 24(12), С. 1177 - 1186

Опубликована: Сен. 14, 2023

Uric acid is a product of purine nucleotide metabolism, and high concentrations uric can lead to hyperuricemia, gout other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine hypoxanthine into acid, has become target for drug development against hyperuricemia gout. Inhibition oxidase reduce production so inhibitors are used treat diseases, including In recent years, researchers have obtained new through design, synthesis, or separation natural products. This paper summarizes research on since 2015, mainly products, pyrimidine derivatives, triazole isonicotinamide chalcone furan coumarin pyrazole imidazole hoping provide valuable information novel inhibitors.

Язык: Английский

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Aldose reductase inhibition properties of novel thiazolidin-2,4-diones: In vitro and in silico approach for the treatment of diabetes-related complications

Journal of Molecular Liquids, Год журнала: 2025, Номер unknown, С. 127487 - 127487

Опубликована: Март 1, 2025

Язык: Английский

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Impairment of electron transport chain and induction of apoptosis by chrysin nanoparticles targeting succinate-ubiquinone oxidoreductase in pancreatic and lung cancer cells

Genes & Nutrition, Год журнала: 2023, Номер 18(1)

Опубликована: Март 11, 2023

Abstract Background Flavonoids may help ameliorate the incidence of major causes tumor-related mortality, such as pancreatic ductal adenocarcinoma (PDAC) and lung cancer, which are predicted to steadily increase between 2020 2030. Here we compared effect chrysin nanoparticles (CCNPs) with 5-fluorouracil (5-FLU) on activity expression mitochondrial complex II (CII) induce apoptosis in (PANC-1) (A549) cancer cells. Methods Chrysin were synthesized characterized, IC 50 was evaluated normal, PANC-1, A549 cell lines using MTT assay. The CCNPs CΙΙ activity, superoxide dismutase mitochondria swelling evaluated. Apoptosis assessed flow cytometry, C D subunits SDH, sirtuin-3 (SIRT-3), hypoxia-inducible factor (HIF-1α) RT-qPCR. Results CII subunit binding determined used evaluate effectiveness treatment SDH ubiquinone oxidoreductase. Enzyme significantly decreased (chrysin < 5-FLU 5-FLU, respectively), confirmed by significant decrease D, SIRT-3, HIF-1α mRNA (CCNPs 5-FLU). There also a apoptotic effects > 5-FLU) both PANC-1 cells respectively) than that non-cancerous Conclusion Treatment improved succinate-ubiquinone oxidoreductase therefore has potential more efficient formulation chemotherapy prevent metastasis angiogenesis targeting PDAC cancer.

Язык: Английский

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Design, synthesis and biological activity determination of novel phenylpyrazole protoporphyrinogen oxidase inhibitor herbicides

Pesticide Biochemistry and Physiology, Год журнала: 2023, Номер 196, С. 105588 - 105588

Опубликована: Авг. 25, 2023

Язык: Английский

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