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

Journal of Molecular Recognition, Год журнала: 2022, Номер 35(12)

Опубликована: Сен. 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.

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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Antioxidant, Antiglaucoma, Anticholinergic, and Antidiabetic Effects of Kiwifruit (Actinidia deliciosa) Oil: Metabolite Profile Analysis Using LC-HR/MS, GC/MS and GC-FID

Life, Год журнала: 2023, Номер 13(9), С. 1939 - 1939

Опубликована: Сен. 20, 2023

Determining the antioxidant abilities and enzyme inhibition profiles of medicinally important plants their oils is great importance for a healthy life treatment some common global diseases. Kiwifruit (Actinidia deliciosa) oil was examined researched using several bioanalytical methods comprehensively first time in this research to determine its antioxidant, antiglaucoma, antidiabetic anti-Alzheimer's capabilities. Additionally, kiwifruit inhibitory effects on acetylcholinesterase (AChE), carbonic anhydrase II (CA II), α-amylase, which are linked number metabolic illnesses, were established. Furthermore, LC-HRMS analysis used assess phenolic content oil. It came light that contained 26 different compounds. According findings, abundant apigenin (74.24 mg/L oil), epigallocatechin (12.89 caryophyllene oxide luteolin (5.49 oil). In addition, GC-MS GC-FID studies ascertain quantity chemical composition essential Squalene (53.04%), linoleoyl chloride (20.28%), linoleic acid (2.67%), palmitic (1.54%) most compounds For radical scavenging activities oil, 1,1-diphenyl-2-picryl-hydrazil (DPPH•) 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) radicals techniques examined. These effectively demonstrated potent properties (IC50: 48.55 μg/mL DPPH•, IC50: 77.00 ABTS•+ scavenging). Also, reducing capabilities, iron (Fe3+), copper (Cu2+), Fe3+-2,4,6-tri(2-pyridyl)-S-triazine (TPTZ) studied. Moreover, showed considerable effect towards hCA 505.83 μg/mL), AChE 12.80 α-amylase 421.02 μg/mL). The results revealed use pharmaceutical procedure has very due anti-Alzheimer, antidiabetic, antiglaucoma effects.

Язык: Английский

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A comprehensive review on the synthesis of substituted piperazine and its novel bio-medicinal applications

Chemistry of Inorganic Materials, Год журнала: 2024, Номер 2, С. 100041 - 100041

Опубликована: Фев. 24, 2024

Piperazine is two nitrogen containing heterocyclic compound. The fundamental activity of the piperazine due to 1,4-position atoms and their substitutions. SN1 reaction followed by others alkylation substitution reactions. Substituted derivatives hold an important position for development crucial drugs. They exhibit a broad spectrum biological activities e.g. antitubercular, antibacterial, anti-inflammatory, anticancer, antiviral, antidiabetic antimalarial. Immense numbers displayed disubstituted are presence in ring. Keeping mind profile, series novel 1,4-substituted synthesized were collected. All prepared expected show different particularly enzyme inhibition against α-Amylase.

Язык: Английский

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Exploring the Inhibitory Effects of Quinolone Medications on Carbonic Anhydrase Enzyme Activity: In Vitro and In Silico Investigation

ChemistrySelect, Год журнала: 2024, Номер 9(30)

Опубликована: Авг. 6, 2024

Abstract Enzyme inhibition is a frequently employed technique for regulating enzyme activity in several biological systems that are physiologically significant. In this study, it was evaluated the effectiveness of six specific quinolone medicines, namely lomefloxacin, nalidixic acid, gatifloxacin, norfloxacin, sparfloxacin and nitrofurantoin, inhibiting two human isoforms carbonic anhydrase (hCA) play role different physiological pathological circumstances. order to achieve objective, both vitro silico investigations were conducted get deeper understanding potential binding interactions affinities hCA I II isoforms. The kinetic inhibitory effects (K i s) ranged from 1.31 13.07 μM, comparison reference medication acetazolamide (AAZ, K 0.12 μM). addition, effectively suppressed by these drugs, with s ranging 1.42 11.93 compared AAZ 0.098 Significant between medicines hCAs indicated their support therapeutic targets against diseases. Furthermore, findings acquired will contribute enhancement dose regimens medications prevention unforeseen drug‐drug when administered concurrently other substances.

Язык: Английский

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Establishing a link between the chemical composition and biological activities of Gladiolus italicus Mill. from the Turkish flora utilizing in vitro , in silico and network pharmacological methodologies

Toxicology Mechanisms and Methods, Год журнала: 2024, Номер unknown, С. 1 - 21

Опубликована: Сен. 8, 2024

Five solvent extracts (n-hexane, ethyl acetate, ethanol, ethanol/water (70%), and water) of

Язык: Английский

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Novel Dibenzoazepine-Substituted Triazole Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors and Anticancer Agents: Synthesis, Characterization, Biological Evaluation, and In Silico Studies

ACS Omega, Год журнала: 2024, Номер 9(47), С. 46860 - 46878

Опубликована: Ноя. 16, 2024

The new dibenzoazepine-substituted triazole hybrids (12–20) were designed by molecular hybridization approach and synthesized utilizing the Cu(I)-catalyzed click reaction. hybrid structures obtained in high yields (74–98%) with a simple two-step synthesis strategy fully characterized. These compounds assessed for their influence on various metabolic enzymes including human carbonic anhydrase isoenzymes (hCA I hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE). Ki values concerning I, II, AChE, BChE ranges 29.94–121.69, 17.72–89.42, 14.09–44.68, 1.15–48.82 nM, respectively. Compound 13 was 49.70-fold more active than tacrine (standard drug) 5.49-fold AChE. 14 4.16-fold acetazolamide 5.79-fold II. cytotoxic effects of products investigated triple-negative breast cancer cell lines. IC50 most effective calculated between 12.51 ± 1.92 18.07 2.14 μM MDA-MB-231 BT-549 cells. Molecular docking ADME predictions performed. Then, vitro analyzed dynamics (MD) simulation MM/GBSA calculation. Consequently, showed good cytotoxicity inhibition potential colony formation

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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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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Evaluation of Carbonic Anhydrase, Acetylcholinesterase, Butyrylcholinesterase, and α-Glycosidase Inhibition Effects and Antioxidant Activity of Baicalin Hydrate

Life, Год журнала: 2023, Номер 13(11), С. 2136 - 2136

Опубликована: Окт. 29, 2023

Baicalin is the foremost prevalent flavonoid found in Scutellaria baicalensis. It also frequently occurs many multi-herbal preparations utilized Eastern countries. The current research has assessed and compared antioxidant, antidiabetic, anticholinergic, antiglaucoma properties of baicalin hydrate. hydrate was tested for its antioxidant capacity using a variety techniques, including N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD•+) scavenging activity, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS•+) 1,1-diphenyl-2-picrylhydrazyl (DPPH•) potassium ferric cyanide reduction ability, cupric ions (Cu2+) reducing activities. Also, comparative purposes, reference antioxidants, such as butylated hydroxyanisole (BHA), Trolox, α-Tocopherol, hydroxytoluene (BHT) were employed. had an IC50 value 13.40 μg/mL (r2: 0.9940) DPPH scavenging, whereas BHA, BHT, α-Tocopherol values 10.10, 25.95, 7.059, 11.31 DPPH• respectively. These findings showed that comparably close similar capability to α-tocopherol, but it performed better than BHT. Additionally, apart from these studies, ability inhibit number metabolic enzymes, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II), α-glycosidase, which have been linked several serious illnesses, Alzheimer's disease (AD), glaucoma, diabetes, where Ki toward aforementioned enzymes 10.01 ± 2.86, 3.50 0.68, 19.25 1.79, 26.98 9.91 nM,

Язык: Английский

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