Synthesis,Spectroscopic Analysis,and in Vitro/in Silico Biological Studies of Novel Piperidine Derivatives Heterocyclic Schiff-Mannich Base Compounds |
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Authors: | Songül Boy Abdülmelik Aras Fikret Türkan Onur Akyıldırım Murat Beytur Halide Sedef Karaman Sevda Manap Haydar Yüksek |
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Affiliation: | 1. Atatürk Vocational College of Health Service, Kafkas University, Kars, 36100 Turkey;2. Department of Biochemistry, Faculty of Science and Arts, Iğdır University, Iğdır, 76100 Turkey;3. Health Services Vocational School, Iğdır University, Iğdır, 76000 Turkey;4. Department of Chemical Engineering, Faculty of Engineering and Architecture, Kafkas University, Kars, 36100 Turkey;5. Department of Chemistry, Faculty of Science and Letters, Kafkas University, Kars, 36100 Turkey;6. Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, 25240 Turkey |
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Abstract: | In the present study, 3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones ( S1-8 ) were synthesized by treating 4-hydroxybenzaldehyde ( B ) with eight different 3-substitued-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones ( T1-8 ) in acetic acid medium, separately. The synthesized Schiff bases ( S ) were reacted with formaldehyde and secondary amine such as 4-piperidinecarboxyamide to afford novel heterocyclic bases. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones ( T ) were treated with 4-piperidinecarboxyamide in the presence of formaldehyde to synthesize eight new 1-(4-piperidinecarboxyamide-1-yl - methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones ( M1-8 ). The structure characterization of compounds was carried out using 1H-NMR, IR, HR-MS, and 13C-NMR spectroscopic methods. The inhibitory properties of the newly synthesized compounds were calculated against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST) enzymes. Ki values were calculated in the range of 20.06±3.11–36.86±6.17 μM for GST, 17.87±2.91–30.53±4.25 μM for AChE, 9.08±0.69–20.02±2.88 μM for BChE, respectively, Besides, IC50 values were also calculated. Best binding scores of -inhibitors against used enzymes were calculated as −12.095 kcal/mol, −12.775 kcal/mol, and −9.336 kcal/mol, respectively. While 5-oxo-triazole piperidine-4-carboxamide moieties have a critical role in the inhibition of AChE and GST enzymes, hydroxy benzyl moiety is important for BChE enzyme inhibition. |
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Keywords: | schiff base heterocyclic bases inhibitory activity docking study 4-piperidinecarboxyamide |
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