Neuroprotective activity of novel phenanthrene derivative from Grewia tiliaefolia by in vitro and in silico studies DOI Creative Commons
Ankita Rajput,

Palvi Sharma,

Nitish Kumar

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Feb. 10, 2023

Abstract Medicinal plants possess range of phytochemicals accountable for their diverse biological activities. Presently, such compounds have been isolated from medicinal plants, characterized and evaluated pharmacological potential. In the present study, efforts made to isolate compound(s) Grewia tiliaefolia Vahl., plant known its ameliorative effect on brain related diseases as anxiety, depression, cognitive disorders Parkinson’s disease. Plant extract was subjected isolation using column chromatography compound by NMR FTIR LCMS. The novel with IUPAC name is propyl 3-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylate, designated A-1 has not reported before. further antioxidant potential in vitro assays (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH assay reducing power assay, RPA). Also, Acetylcholinesterase (AChE) inhibitory analysed. Results showed that exhibited significantly higher activity both RPA compared extract. case AChE again, shown silico study conducted predict action proteins playing crucial role neurological neurodegenerative gamma amino butyric acid (GABA) receptor glutamate α amino-3-hydroxyl-5-methyl-4-isoxazolepropionic (Glu AMPA) epilepsy enzyme Alzheimer’s diseases. interaction following order: > GABA Glu AMPA receptor. Further, molecular dynamic simulations ADME studies revealed yielded good results all parameters hence can relieve like symptoms.

Language: Английский

Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif DOI
Yeliz Demir, Cüneyt Türkeş, M. Serdar Çavuş

et al.

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

Citations

42
Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors DOI
Feyzi Sinan Tokalı, Yeliz Demir, Cüneyt Türkeş

et al.

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

Citations

40
A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations DOI
Hasan Yakan, Halit Muğlu, Cüneyt Türkeş

et al.

Journal of Molecular Structure, Journal Year: 2023, Volume and Issue: 1280, P. 135077 - 135077

Published: Feb. 1, 2023

Language: Английский

Citations

29
N‐substituted phthalazine sulfonamide derivatives as non‐classical aldose reductase inhibitors DOI
Cüneyt Türkeş, Mustafa Arslan, Yeliz Demir

et al.

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

Citations

33
Exploration of Some Bis‐Sulfide and Bis‐Sulfone Derivatives as Non‐Classical Aldose Reductase İnhibitors DOI
Cüneyt Türkeş, Yeliz Demir, Abdullah Biçer

et al.

ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(5)

Published: Feb. 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.

Language: Английский

Citations

19
Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as multitarget acetylcholinesterase and carbonic anhydrase inhibitors DOI
Samet Mert, Yeliz Demir, Yusuf Sert

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1319, P. 139472 - 139472

Published: July 26, 2024

Language: Английский

Citations

7
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 DOI
Gökhan Zengin, Mehmet Veysi Çetiz, Nurgül Abul

et al.

Toxicology Mechanisms and Methods, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Sept. 8, 2024

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

Language: Английский

Citations

6
In Vitro Inhibitory Activity and Molecular Docking Study of Selected Natural Phenolic Compounds as AR and SDH Inhibitors** DOI Open Access
Cüneyt Türkeş, Yeliz Demir, Şükrü Beydemir

et al.

ChemistrySelect, Journal Year: 2022, Volume and Issue: 7(48)

Published: Dec. 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.

Language: Английский

Citations

24
A new series of hydrazones as small‐molecule aldose reductase inhibitors DOI
Mehlika Dilek Altıntop, Yeliz Demir, Cüneyt Türkeş

et al.

Archiv der Pharmazie, Journal Year: 2023, Volume and Issue: 356(4)

Published: Jan. 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.

Language: Английский

Citations

14
“Challenges and toxicity assessment of inorganic nanomaterials in biomedical applications: Current status and future roadmaps” DOI
Pranjali Mahamuni‐Badiger, Maruti J. Dhanavade

Journal of Drug Delivery Science and Technology, Journal Year: 2023, Volume and Issue: 87, P. 104806 - 104806

Published: Aug. 1, 2023

Language: Английский

Citations

13