Antioxidant and anticholinesterase potentials of novel 4,6-dimethoxyindole based unsymmetrical azines: Synthesis, molecular modeling, in silico ADME prediction and biological evaluations
Yükleniyor...
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Taylor and Francis Ltd.
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Chemically and biologically important -C = N-N = C- diimine linkage was used to build unsymmetrical azine systems with indole heterocyclic backbone and substituted aromatic carbaldehydes. Ten novel compounds 7a-j were synthesized by the Schiff base reaction of 4,6-dimethoxyindole-7-hydrazone 5 and a range of substituted carbaldehydes 6a-j with high yields and purities. The biological study was directed to identify the antioxidant potentials due to the expected electronic delocalization capability of designated linkage which is important for possible hydrogen or electron donation. The three different assays, namely DPPH free radical scavenging, ABTS cationic radical decolarization and CUPRAC (cupric reducing antioxidant capacity) were employed to detect the antioxidant properties. The antioxidant potentials were found to be moderate for ABTS and CUPRAC assays and the compound 7j was the most potent candidate for all the antioxidant assays. More importantly, the anticholinesterase properties were investigated by acetylcholinesterase (ACh) and butyrylcholinesterase (BCh) enzyme inhibition assays. The molecular docking studies were also carried out to determine the possible poses of ligands 7a-j in binding sites of enzymes and ligand-residue interactions. The synthesized compounds were found to be more effective for the anticholinesterase activity with three promising candidates 7d, 7h and 7j in the case of BChE inhibitions. The compound 7h was determined as the best candidate with the comparable IC50 values for AChE and better inhibition potency for BChE with 7j. A range of hydrophobic and hydrophilic interactions were detected for the designated compound 7h and 7j through different amino acid residues and the computational results were found to be compatible with the biological counterparts.
Açıklama
Anahtar Kelimeler
ADME properties, Anticholinesterase, Antioxidant, Indole azines, Molecular modeling
Kaynak
Polycyclic Aromatic Compounds
WoS Q Değeri
N/A
Scopus Q Değeri
Q2
Cilt
Article in Press
Sayı
Künye
Bingül, M., Ercan, S., Boğa, M. ve Bingül, A. A. (2023). Antioxidant and anticholinesterase potentials of novel 4,6-dimethoxyindole based unsymmetrical azines: Synthesis, molecular modeling, in silico ADME prediction and biological evaluations. Polycyclic Aromatic Compounds, Article in Press.
