Sürdürülebilir Kalkınma Amaçları

• 2

• MakaleYalnız künye2026Scopus SJRQ2/r/kostu/10419
  Synthesis, biological evaluation, and computational analysis of chromone-based carboxamides targeting Alzheimer’s disease

  Kilic, Burcu; Aksakal, Fatma; Dogruer, Deniz S.

  Alzheimer's disease (AD) is among the most serious long-term health problems of the last few decades. Regrettably, the current lack of treatment options for AD has made it a highly sought-after topic of drug development research. The utilization of multitarget directed ligand design (MTDL) has been the primary focus of research on developing pharmaceuticals for AD. By this approach, we designed novel cholinesterase inhibitors (ChEI) that may also exhibit additional monoamine oxidase (MAO) inhibitory, antioxidant, and metal chelator properties. Within the scope of the current work, twenty N-(2-(tertiaryamine-substituted)ethyl)-4-oxo-4H-chromene-2/3-carboxamide derivatives were synthesized and characterized. Subsequently, we conducted biological investigations for enzyme inhibitory (ChEs and MAO), antioxidant, and metal-chelating activities. Furthermore, we assessed the in silico physicochemical parameters of the compounds to evaluate their drug-likeness or druggability. Additionally, comprehensive computational studies were conducted, including density functional theory (DFT)-based frontier molecular orbital (FMO) analysis, global chemical reactivity descriptors, and molecular electrostatic potential (MEP) surface analysis, along with molecular docking, to elucidate the electronic properties, reactive sites, and binding interactions of the compounds with ChE enzymes.

  • 
  İncele
• MakaleYalnız künye2024Scopus SJRQ2/r/kostu/10247
  Multifunctional anti-Alzheimer's agents: Synthesis, biological evaluation, and molecular docking study of new 2-phenoxyacetamide/3-phenoxypropanamide/4-oxobutanamide derivatives

  Shakila, Shakila; Kilic, Burcu; Bardakkaya, Merve; Aksakal, Fatma; Sagkan, Rahsan Ilikci; Dogruer, Deniz S.

  In the current study, three series of new compounds were designed and synthesized through hit optimization, based on the hit compound with a structure (E)-N-(4-{[benzyl(methyl)amino]methyl}thiazol-2-yl)-3-(3,4-dimethoxyphenyl)prop‑2-enamide, which was found as a potential multifunctional anti-Alzheimer agent in our previous study. Then, the biological activities of synthesized compounds (4a-c, 13a-b and 15a-c) were evaluated. The results indicated that 4b, a 2-phenoxyacetamide derivative, exhibited good multifunctional activities. Namely, compound 4b displayed better BChE inhibition (BChE IC50 = 2.10 µM) and antioxidant activity (ORAC = 1.18 Trolox equivalents) compared to the hit compound (BChE IC50 = 14.70 µM, ORAC = 0.5 Trolox equivalents). Additionally, 4b was able to chelate all tested biometals and it also exhibited a neuroprotective effect (63 %), comparable to reference ferulic acid (77 %) while maintaining its safety upon PC12 cell line. When it comes to lowering the levels of TNF-α, NO, IL-1β, and IL-6, 4b performed better activity, relative to the other synthesized compounds. Subsequently, in silico studies such as physicochemical properties, density functional theory (DFT) computational approach and molecular docking studies were performed.

  • 
  AtıfScopus2·WoS2·OpenAlex3

  İncele