Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma,Alzheimer's Disease and Diabetes Mellitus |
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Authors: | Dr Feyzi Sinan Tokalı Dr Parham Taslimi Dr Burak Tuzun Dr Ahmet Karakuş Dr Nastaran Sadeghian Prof Dr İlhami Gulçin |
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Institution: | 1. Department of Material and Material Processing Technologies, Kars Vocational School, Kafkas University, Kars, 36100 Turkiye;2. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, 74100 Turkiye;3. Departmentof Plant and Animal Production, Sivas Technical Sciences Vocational School, Sivas Cumhuriyet University, 58140 Sivas, Turkiye;4. Department of Chemistry, Faculty of Sciences, Atatürk University, 25240- Erzurum, Turkiye |
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Abstract: | Quinazolinones, which represent an important part of nitrogen-containing six-membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from the reaction of acylated derivatives of 4-hydroxy benzaldehyde with 3-amino-2-alkylquinazolin-4(3H)-ones with good yields (85–94 %) and their structures were characterized using Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (1H-NMR, 13C-NMR), and High-Resolution Mass Spectroscopy (HR-MS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on α-Glucosidase (α-Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Carbonic anhydrase I–II (hCA I–II) metabolic enzymes were investigated. All compounds showed inhibition at nanomolar level with the Ki values in the range of 12.73±1.26–93.42±9.44 nM for AChE, 8.48±0.92–25.84±2.59 nM for BChE, 66.17±5.16–818.06±44.41 for α-Glu, 2.56±0.26–88.23±9.72 nM for hCA I, and 1.68±0.14–85.43±7.41 nM for hCA II. Molecular docking study was performed to understand the interactions of the most potent compounds with corresponding enzymes. Also, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties of the compounds were investigated. |
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Keywords: | cholinesterases diabetes quinazolin-4(3H)-one molecular docking ADME/T |
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