Structural characterization and biological evaluation of uracil-appended benzylic amines as acetylcholinesterase and carbonic anhydrase I and II inhibitors

Bulut, Zafer; Abul, Nurgül; Poslu, Ayşe Halıç; Gülçın, İlhami; Ece, Abdulillah; Erçağ, Erol; Koz, Ömer; Koz, Gamze

doi:10.1016/j.molstruc.2023.135047

Cited by 16 publications

(15 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Computer-aided drug design tools provide a detailed picture of the biologically active molecules at the molecular level. Our recent successful in silico studies − prompted us to confer molecular docking simulations as a tool to enlighten binding conformations of the ligands.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Evaluation of a New Series of Hydrazones as Small-Molecule Akt Inhibitors for NSCLC Therapy

Erdönmez,

Altıntop,

Akalın Çiftçi

et al. 2023

ACS Omega

Self Cite

View full text Add to dashboard Cite

In an endeavor to identify small molecules for the management of non-small-cell lung carcinoma, 10 new hydrazone derivatives (3a–j) were synthesized. MTT test was conducted to examine their cytotoxic activities against human lung adenocarcinoma (A549) and mouse embryonic fibroblast (L929) cells. Compounds 3a, 3e, 3g, and 3i were determined as selective antitumor agents on A549 cell line. Further studies were conducted to figure out their mode of action. Compounds 3a and 3g markedly induced apoptosis in A549 cells. However, both compounds did not show any significant inhibitory effect on Akt. On the other hand, in vitro experiments suggest that compounds 3e and 3i are potential anti-NSCLC agents acting through Akt inhibition. Furthermore, molecular docking studies revealed a unique binding mode for compound 3i (the strongest Akt inhibitor in this series), which interacts with both hinge region and acidic pocket of Akt2. However, it is understood that compounds 3a and 3g exert their cytotoxic and apoptotic effects on A549 cells via different pathway(s).

show abstract

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Evaluation of a New Series of Hydrazones as Small-Molecule Akt Inhibitors for NSCLC Therapy

Erdönmez,

Altıntop,

Akalın Çiftçi

et al. 2023

ACS Omega

Self Cite

View full text Add to dashboard Cite

show abstract

“…Subsequently, DTNB solution (0.5 mM, 50 μL) was added, and the reaction was initiated by introducing acetylthiocholine iodide solution (10 mM, 50 μL). Finally, the absorbance values of the samples were measured at 412 nm [56,57] . Tacrine was employed as a positive control in the present study.…”

Section: Methodsmentioning

confidence: 99%

“…The quantity of the released product is determined spectrophotometrically. The activity of the isozymes is determined by measuring the absorbance changes in a kinetic mode for three minutes at 348 nm and a temperature of 25 °C [44,57] . In this study, a positive control was acetazolamide.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro and in Silico Studies of 3‐Hydroxyflavone‐Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α‐Glycosidase Inhibitors

Guney,

Aggul,

Erturk

et al. 2023

ChemistrySelect

View full text Add to dashboard Cite

In this study, a novel series of sulfonate esters derived from 3‐hydroxyflavone was synthesized and their inhibitory effects on acetylcholinesterase (AChE), α‐glycosidase (AG), and carbonic anhydrase I and II (hCA I and II) enzymes were investigated using experimental and molecular docking analyses. The synthesis involved the reaction of 3‐hydroxyflavone with tosyl chloride, mesytl chloride, β‐naphthylsulfonyl chloride, and 8‐quinolinesulfonyl chloride. The characterization of each compound was confirmed by obtaining 1H NMR, 13C NMR and IR spectra. Furthermore, IC50 and Ki values for the synthesized compounds were calculated and compared to the clinical enzyme inhibitors. Our results showed that the synthesized compounds exhibited inhibition against the targeted enzymes, with Ki values ranging from 1.92 to 4.16 nM for AChE, 32.40 to 55.49 nM for AG, 9.45 to 65.53 nM for hCA I, and 76.62 to 163.33 nM for hCA II. The compound involved quinolinesulfonyl moiety demonstrated especially potent inhibition with IC50 values of 3.96 nM for AChE, 32.40 nM for AG, 9.50 nM for hCA I, and 76.62 nM for hCA II. The docking results aligned well with our experimental findings. The findings have promising implications for the development of novel inhibitors and drug discovery efforts in the future.

show abstract

“…It is thought that these disorders can be cured by inhibiting the essential enzymes linked to them. However, the synthetic drugs that are used to inhibit these important enzymes have a lot of negative side effects [ 27 ]. Researchers were encouraged to find an alternative natural product with fewer or no negative effects in an effort to solve this issue [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Determination of Antioxidant, Anti-Alzheimer, Antidiabetic, Antiglaucoma and Antimicrobial Effects of Zivzik Pomegranate (Punica granatum)—A Chemical Profiling by LC-MS/MS

Karageçili

İzol

Kıreçcı

et al. 2023

Life

View full text Add to dashboard Cite

Zivzik pomegranate (Punica granatum) has recently sparked considerable interest due to its nutritional and antioxidant properties. To evaluate the antioxidant capacities of P. granatum juice, ethanol (EEZP), and water (WEZP) extracts from peel and seed, the antioxidant methods of 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid radical (ABTS•+) scavenging, 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH•) scavenging, Fe3+-2,4,6-tris(2-pyridyl)-S-triazine (TPTZ) reducing, Fe3+ reducing, and Cu2+ reducing methods were used. The antioxidant capacities of samples were compared with the most commonly used synthetic antioxidants, i.e., BHA, BHT, α-tocopherol, and Trolox. In terms of setting an example, the IC50 values of EEZP for ABTS•+ and DPPH• scavenging activities were found to be lower than standards, at 5.9 and 16.1 μg/mL, respectively. The phenolic and flavonoid contents in EEZP peel were 59.7 mg GAE/g and 88.0 mg QE/g, respectively. Inhibition of α-glycosidase, α-amylase, acetylcholinesterase, and human carbonic anhydrase II (hCA II) enzymes was also investigated. EEZP demonstrated IC50 values of 7.3 μg/mL against α-glycosidase, 317.7 μg/mL against α-amylase, 19.7 μg/mL against acetylcholinesterase (AChE), and 106.3 μg/mL against CA II enzymes. A total of 53 phenolic compounds were scanned, and 30 compounds were determined using LC-MS/MS. E. coli and S. aureus bacteria were resistant to all four antibiotics used as standards in hospitals.

show abstract

Structural characterization and biological evaluation of uracil-appended benzylic amines as acetylcholinesterase and carbonic anhydrase I and II inhibitors

Cited by 16 publications

References 49 publications

Design, Synthesis, and Evaluation of a New Series of Hydrazones as Small-Molecule Akt Inhibitors for NSCLC Therapy

Design, Synthesis, and Evaluation of a New Series of Hydrazones as Small-Molecule Akt Inhibitors for NSCLC Therapy

In Vitro and in Silico Studies of 3‐Hydroxyflavone‐Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α‐Glycosidase Inhibitors

Determination of Antioxidant, Anti-Alzheimer, Antidiabetic, Antiglaucoma and Antimicrobial Effects of Zivzik Pomegranate (Punica granatum)—A Chemical Profiling by LC-MS/MS

Contact Info

Product

Resources

About