Synthesis and Structure of Novel Hybrid Compounds Containing Phthalazin-1(2H)-imine and 4,5-Dihydro-1H-imidazole Cores and Their Sulfonyl Derivatives with Potential Biological Activities DOI Open Access
Łukasz Balewski, М. Gdaniec, Anna Hering

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11495 - 11495

Published: Oct. 26, 2024

A novel hybrid compound—2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (5) was synthesized and converted into di-substituted sulfonamide derivatives 6a–o phthalazine ring opening products—hydrazonomethylbenzonitriles 7a–m. The newly prepared compounds were characterized using elemental analyses, IR NMR spectroscopy, as well mass spectrometry. Single crystal X-ray diffraction data collected for the representative 5, 6c, 6e, 7g, 7k. antiproliferative activity of compound sulfonyl benzonitriles 7a–m evaluated on approximately sixty cell lines within nine tumor-type subpanels, including leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate, breast. None tested showed any against cancer used. antioxidant properties all assessed DPPH, ABTS, FRAP radical scavenging methods, β-carotene bleaching test. Antiradical tests revealed that among investigated compounds, a moderate ABTS antiradical effect observed 6j (IC50 = 52.77 µg/mL). Benzonitrile 7i bearing two chlorine atoms phenyl system in test 86.21 Finally, interaction AGE/RAGE presence selected phthalazinimines 6a, 6b, 6g, 6m, hydrazonomethylbenzonitriles 7a, 7c–g, 7i–k determined by ELISA assay. inhibitory potency toward RAGE found hydrazonomethylbenzonitriles—7d with an electron-donating methoxy group (R 3-CH3O-C6H4) 7f, 7k electron-withdrawing substituent (7f, R 2-Cl-C6H4; 7k, 4-NO2-C6H4).

Language: Английский

Novel spiroindoline derivatives targeting aldose reductase against diabetic complications: Bioactivity, cytotoxicity, and molecular modeling studies DOI
Özcan Güleç, Cüneyt Türkeş, Mustafa Arslan

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 145, P. 107221 - 107221

Published: Feb. 19, 2024

Language: Английский

Citations

48
Insights into Manganese Superoxide Dismutase and Human Diseases DOI Open Access
Mengfan Liu, Xueyang Sun,

Boya Chen

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 15893 - 15893

Published: Dec. 14, 2022

Redox equilibria and the modulation of redox signalling play crucial roles in physiological processes. Overproduction reactive oxygen species (ROS) disrupts body's antioxidant defence, compromising homeostasis increasing oxidative stress, leading to development several diseases. Manganese superoxide dismutase (MnSOD) is a principal enzyme that protects cells from damage by converting anion radicals hydrogen peroxide mitochondria. Systematic studies have demonstrated MnSOD plays an indispensable role multiple This review focuses on preclinical evidence describes mechanisms diseases accompanied with imbalanced status, including fibrotic diseases, inflammation, diabetes, vascular neurodegenerative cancer. The potential therapeutic effects activators mimetics are also discussed. Targeting this specific radical scavenger may be clinically beneficial strategy, understanding provide positive insight into preventing treating related

Language: Английский

Citations

67
Novel bis-ureido-substituted sulfaguanidines and sulfisoxazoles as carbonic anhydrase and acetylcholinesterase inhibitors DOI
Nebih Lolak, Süleyman Akocak, Mustafa Durgun

et al.

Molecular Diversity, Journal Year: 2022, Volume and Issue: 27(4), P. 1735 - 1749

Published: Sept. 22, 2022

Language: Английский

Citations

51
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
Astragalus Polysaccharide Ameliorates Renal Inflammatory Responses in a Diabetic Nephropathy by Suppressing the TLR4/NF-κB Pathway DOI Creative Commons
Mingfei Guo, Jiarong Gao, Lei Jiang

et al.

Drug Design Development and Therapy, Journal Year: 2023, Volume and Issue: Volume 17, P. 2107 - 2118

Published: July 1, 2023

Diabetic nephropathy (DN), as a chronic inflammatory complication of diabetes, is characterized by hyperglycemia, albuminuria and edema, which ultimately becomes the leading cause end-stage renal disease (ESRD). Astragalus polysaccharide (APS), extracted from membranaceus, was widely used in treatment diabetes mellitus. However, functional roles APS ameliorate responses DN, remain poorly understood. Therefore, purpose this study to explore molecular mechanism on DN vivo vitro models. We explored beneficial effects streptozotocin (STZ)-induced rat model high glucose (HG)-treated glomerular podocyte model. The fasting blood (FBG) ratio kidney weight body were measured after 4 weeks treatment. injury parameters containing serum creatinine (Scr), urea nitrogen (BUN) 24 h urinary protein evaluated. pathological examination observed hematoxylin-eosin (HE) staining. levels IL-1β, IL-6 MCP-1 evaluated ELISA assay. proliferation podocytes determined using CCK-8 assay flow cytometry. qRT-PCR Western blot analysis performed determine amounts TLR4/NF-κB-related gene expression. Our results indicated that effectively decreased FBG, BUN, Scr damage when compared with STZ-induced group. Additionally, significantly ameliorated reducing cytokines IL-6, expression inhibiting TLR4/NF-κB pathway activity rats. Consistent vitro, HG-induced response also alleviated through administration. found injury, mechanisms perhaps related relieving attenuating signaling pathway.

Language: Английский

Citations

24
Aldose reductase with quinolone antibiotics interaction: In vitro and in silico approach of its relationship with diabetic complications DOI
Cüneyt Türkeş

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: unknown, P. 110161 - 110161

Published: Sept. 1, 2024

Language: Английский

Citations

7
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