Sürdürülebilir Kalkınma Amaçları

• 2

Yazarlar

• Topal, Fevzi(2)
• Akocak, Suleyman(1)
• Beydemir, Sukru(1)
• Beydemir, Şükrü(1)
• Durgun, Mustafa(1)
• Isik, Mesut(1)
• Işık, Mesut(1)
• Koçyigit, Umit Muhammet(1)
• Kırboğa, Kevser Kübra(1)
• Lolak, Nebih(1)
• Topal, Meryem(1)
• Türkes, Cueneyt(1)
• Çevik, Ulviye Acar(1)
• Ünver, Hakan(1)

• MakaleAçık Erişim2027Scopus SJRQ2/r/gumushane/13442
  Design, Synthesis, and X-ray Characterization of Benzohydrazide Derivatives as Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease: An Experimental and Computational Approach to Biological Activity

  Topal, Fevzi; Ünver, Hakan; Topal, Meryem; Çevik, Ulviye Acar; Kırboğa, Kevser Kübra; Işık, Mesut; Beydemir, Şükrü

  In this study, a series of new benzohydrazide derivatives (1a-i) were synthesized, and characterized as potential cholinesterase inhibitors for use in the treatment of Alzheimer’s disease (AD). The inhibitory activities of the synthesized compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were evaluated using in vitro and in silico methods. IC50 values for AChE inhibition ranged from 29.50 to 46.21 nM, with compound 1c exhibiting the highest inhibitory potential at an IC50 of 29.50 nM. For the BChE enzyme, the strongest effect was observed with compound 1d at an IC50 of 55 nM. The synthesized derivatives exhibited higher inhibitory potential compared to the reference tacrine (IC50: 58.73 nM for AChE and 187.30 nM for BChE) against cholinesterase enzymes through both competitive and non-competitive inhibition mechanisms. Molecular docking (ΔG: -10.67 to -9.95 kcal/mol for AChE; -9.80 to -8.69 kcal/mol for BChE) and 100 ns molecular dynamics simulations supported the binding affinities and indicated the dynamic stability of the enzyme-inhibitor complexes, in agreement with the experimental inhibition data. In silico ADMET profiling indicated favourable drug-likeness and high predicted gastrointestinal absorption and blood-brain barrier permeability (TPSA 41.46-61.69 A2), and structural alert screening returned no PAINS matches. The findings suggest that these derivatives may serve as promising lead compounds for further investigation as potential cholinesterase inhibitors relevant to AD, pending experimental cytotoxicity evaluation.

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• MakaleAçık Erişim2024Scopus SJRQ3/r/gumushane/10527
  Design and Synthesis of Pyrazole Carboxamide Derivatives as Selective Cholinesterase and Carbonic Anhydrase Inhibitors: Molecular Docking and Biological Evaluation

  Durgun, Mustafa; Akocak, Suleyman; Lolak, Nebih; Topal, Fevzi; Koçyigit, Umit Muhammet; Türkes, Cueneyt; Isik, Mesut; Beydemir, Sukru

  The present study focused on the synthesis and characterization of novel pyrazole carboxamide derivatives (SA1-12). The inhibitory effect of the compounds on cholinesterases (ChEs; AChE and BChE) and carbonic anhydrases (hCAs; hCA I and hCA II) isoenzymes were screened as in vitro. These series compounds have been identified as potential inhibitors with a KI values in the range of 10.69 +/- 1.27-70.87 +/- 8.11 nM for hCA I, 20.01 +/- 3.48-56.63 +/- 6.41 nM for hCA II, 6.60 +/- 0.62-14.15 +/- 1.09 nM for acetylcholinesterase (AChE) and 54.87 +/- 7.76-137.20 +/- 9.61 nM for butyrylcholinesterase (BChE). These compounds have a more effective inhibition effect when compared to the reference compounds. In addition, the potential binding positions of the compounds with high affinity for ChE and hCAs were demonstrated by in silico methods. The results of in silico and in vitro studies support each other. As a result of the present study, the compounds with high inhibitory activity for metabolic enzymes, such as ChE and hCA were designed. The compounds may be potential alternative agents used as selective ChE and hCA inhibitors in the treatment of Alzheimer ' s disease and glaucoma. image

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  AtıfScopus28·WoS28·OpenAlex27

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