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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Novel benzenesulfonamides containing dual triazole moiety with selective carbonic anhydrase inhibition and anticancer activity

RSC Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

A series of sulfonamides incorporating a 1,2,3-triazolyloxime substituted 1,2,3-triazolyl moiety were conceptualized and synthesized as human carbonic anhydrase (

Язык: Английский

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Biological evaluation and in silico study of benzohydrazide derivatives as paraoxonase 1 inhibitors

Journal of Biochemical and Molecular Toxicology, Год журнала: 2022, Номер 36(11)

Опубликована: Авг. 2, 2022

Serum paraoxonase 1 (PON1) is found in all mammalian species and a calcium-dependent hydrolytic enzyme. PON1 hydrolyze several substrates, including carbonates, esters, organophosphates. In the current study, we aimed to investigate effect of presynthesized benzohydrazide derivatives (1-9) on activity. Benzohydrazide compounds moderate inhibited with half-maximal inhibitory concentration values ranging from 76.04 ± 13.51 221.70 13.59 μM KI 38.75 12.21 543.50 69.76 μM. Compound 4 (2-amino-4-chlorobenzohydrazide) showed best inhibition (KI = μM). Molecular docking ADME-Tox studies were also carried out. this context, hope that results obtained study contribute determination side effects new benzohydrazide-based pharmacological be developed.

Язык: Английский

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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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Carvacrol protects against λ‐Cyhalothrin‐induced hepatotoxicity and nephrotoxicity by modulating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy

Environmental Toxicology, Год журнала: 2023, Номер 38(7), С. 1535 - 1547

Опубликована: Март 22, 2023

Abstract λ‐Cyhalothrin, a type II synthetic pyrethroid, has been widely used in households, agriculture, public health, and gardening to control insect pests. Despite its widespread usage, it is known induce variety of adverse effects, including hepatotoxicity nephrotoxicity. The goal this study was investigate the protective effect carvacrol, which antioxidant, anti‐inflammatory, anti‐apoptotic, some other properties, on λ‐Cyhalothrin‐induced nephrotoxicity 35 male Sprague–Dawley rats were randomly divided into five groups for purpose: I‐Control group: II‐CRV group (50 mg/kg carvacrol), III‐LCT (6.23 LCT), IV‐LCT + CRV 25 LCT V‐LCT 50 carvacrol). Using biochemical, real‐time PCR, western blotting methods, collected tissues analyzed. While λ‐Cyhalothrin treatment increased MDA levels, are indicated lipid peroxidation, but reduced SOD, CAT, GPx activities, GSH levels. After receiving carvacrol therapy, degree oxidative stress as values these parameters approached those group. Increased inflammation, apoptosis, endoplasmic reticulum stress, autophagy with administration co‐administration, liver kidney protected from damage, depending stress. considering all data, discovered that kidneys; however, damage. Our findings indicate may be promising agent

Язык: Английский

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Methyl benzoate derivatives: in vitro Paraoxonase 1 inhibition and in silico studies

Journal of Biochemical and Molecular Toxicology, Год журнала: 2022, Номер 36(10)

Опубликована: Июнь 16, 2022

Abstract Paraoxonase 1 (PON1) can metabolize some compounds such as aromatic carboxylic acid and unsaturated aliphatic esters, arylesters, cyclic carbonate, plucuronide drugs, carbamate insecticide classes, nerve gases, lactone compounds. Methyl benzoate has recently been shown to display potent toxicity against several insect species. In the current study, we aimed investigate effect of methyl ( 1–17 ) on PON1 activity. inhibited with K I values ranging from 25.10 ± 4.73 502.10 64.72 μM. Compound 10 (methyl 4‐amino‐2‐bromo benzoate) showed best inhibition = μM). Furthermore, using ADME‐Tox, Glide XP, MM‐GBSA tools Schrödinger Suite 2021‐4, a complete ligand–receptor interaction prediction was performed characterize benzoates ), probable binding modalities versus PON1.

Язык: Английский

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Molecular Docking Studies and the Effect of Fluorophenylthiourea Derivatives on Glutathione‐Dependent Enzymes

Chemistry & Biodiversity, Год журнала: 2022, Номер 20(1)

Опубликована: Дек. 20, 2022

Cancer is a serious problem affecting the health of all human societies. Chemotherapy refers to use drugs kill cancer or origin cancer. In past three decades, researchers have studied about proteins and their roles in production cells. Glutathione S-transferases (GSTs) are superfamily enzymes that play key role cellular detoxification, protecting against reactive electrophiles attacks, including chemotherapeutic agents. reductase (GR) an important antioxidant enzyme involved cell oxidative stress. this current study, GST GR were purified from erythrocytes using affinity chromatography. was obtained with specific activity 5.95 EU/mg protein 52.38 % yield. 4.88 74.88 The effect fluorophenylthiourea derivatives on investigated. Afterward, KI values found range 23.04±4.37 μM-59.97±13.45 μM for 7.22±1.64 μM-41.24±2.55 GST. 1-(2,6-difluorophenyl)thiourea showed best inhibition both enzymes. relationships inhibitors 3D structures explained by molecular docking studies.

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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Determination of Antioxidant Activity, Vitamin C Content, GST Enzyme Inhibition and Phenolic Profile by LC-HRMS of Jujube Fruit and Seed

Deleted Journal, Год журнала: 2025, Номер 67(1)

Опубликована: Янв. 3, 2025

Jujube belongs to the Rhamnaceae family and is known as red date or Chinese date. It has widespread uses due its high nutritional values. In this study, jujube fruit seeds grown in Sakarya, Turkey, were extracted their total phenolic flavonoid contents evaluated. The liquid chromatography-high resolution mass spectrometry (LC-HRMS) analyses results showed that 15 different substances identified fruit, while 27 detected seeds. of seed determined 127.91 ± 3.05 mg GAE/g extract (ext) 14.58 5.22 catechin/mg ext., respectively. Moreover, antioxidant glutathione-s-transferase activity extracts also investigated. had a strong effect (IC50 = 81.76 3.56 μg/mL for DPPH; IC50 58.99 0.70 ABTS). Furthermore, inhibitory against enzyme.

Язык: Английский

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Isoindole‐1,3‐Dione Sulfonamides as Potent Inhibitors of Glucosidase, Aldose Reductase, and Tyrosinase: A Molecular Docking and Enzyme Inhibition Study

Biotechnology and Applied Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Diabetes mellitus, especially type 2, is a global health challenge, and effective enzyme inhibitors are essential for its control. Conventional have drawbacks such as gastrointestinal side effects regional availability, examples being acarbose epalrestat. Moreover, tyrosinase, which controls melanin synthesis also target reducing hyperpigmentation disorders. In this study, we demonstrate the inhibitory action of novel isoindole-1,3-dione-based sulfonamides against key enzymes associated with diabetes hyperpigmentation, α-Glucosidase (α-Glu), aldose reductase (ALR2), tyrosinase. The presynthesized compounds (3, 4a-k) tested in vitro inhibition α-Glu, ALR2, tyrosinase compared reference acarbose, epalrestat, kojic acid. Kinetic studies showed that both competitive noncompetitive modes were observed. Among them, compound 4a displayed highest ALR2 potency (Ki: 0.211 µM) was superior to terms 4k shown be more potent Ki 0.049 µM, particularly versus acarbose. Compound 4d excellent activity 1.43 assays, much than Molecular docking revealed details enzyme-binding interactions, justify respective mechanisms Structure-activity relationships reflected strong hydrogen bonding hydrophobic interactions led higher potency. These findings highlight importance therapeutic agents will provide valuable leads developing multifunctional diabetic complications hyperpigmentation.

Язык: Английский

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