Synthesis, Spectroscopic Analysis, and <i>in Vitro/in Silico</i> Biological Studies of Novel Piperidine Derivatives Heterocyclic Schiff‐Mannich Base Compounds
Songül Boy, Abdülmelik Aras, Fikret Türkan, Onur Akyıldırım, Murat Beytur, Halide Sedef Karaman, Sevda Manap, Haydar Yüksek
Abstract
Abstract In the present study, 3‐substitued‐4‐(4‐hydroxybenzylidenamino)‐4,5‐dihydro‐1 H ‐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‐1 H ‐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‐1 H ‐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‐1 H ‐1,2,4‐triazol‐5‐ones ( M1‐8 ). The structure characterization of compounds was carried out using 1 H‐NMR, IR, HR‐MS, and 13 C‐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, IC 50 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.