New piperidine-hydrazone derivatives: Synthesis, biological evaluations and molecular docking studies as AChE and BChE inhibitors.
Hydrazones and the piperidine ring containing compounds were considered as beneficial substrates in drug design. Therefore, this study was aimed at the synthesis of new benzoyl hydrazones derived from ethyl 4-oxopiperidine-1-carboxylate and 2,6-diphenylpiperidin-4-one. The synthesized compounds (1-19) were screened for their antioxidant, anticholinesterase and anticancer activities. The antioxidant capacity of the compounds was evaluated by using four complementary tests. The results showed that compound 7 and 17 have the higher lipid peroxidation inhibitory activity than the other compounds. In DPPH˙ scavenging assay, compounds 5, 6, 10, 14, 17 demonstrated better activity than that of standard BHT, while in ABTS+˙ scavenging assay compound 6 and 17 exhibited better activity among the other compounds. The CUPRAC assay disclosed that compound 2 displayed better activity than α-tocopherol. The anticholinesterase activity was performed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Compound 11 (IC50: 35.30 ± 1.11 μM) inhibited BChE better than galantamine (IC50: 46.03 ± 0.14 μM). We conclude that the compound 11 can be considered as a candidate for BChE inhibitor. Moreover docking method was applied to elucidate the AChE and BChE inhibitory mechanism of the compound 11. Molecular docking analysis revealed that compound 11 bound to BChE enzyme more efficiently when compared to the AChE due to its orientations and different types of interactions. In addition, the non-cytotoxic properties of the compounds brought them into prominence, although they did not show significant anticancer properties.
Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep, Turkey.
Nurcan
N
Karaman
Department of Herbal and Animal Production, Köyceğiz Vocational School, Muğla Sıtkı Koçman University, Muğla, Turkey; Department of Chemistry, Faculty of Sciences, Muğla Sıtkı Koçman University, Muğla, Turkey.
Yusuf
Y
Sıcak
Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep, Turkey.
Tuğba
T
Taşkın-Tok
Department of Chemistry, Faculty of Sciences, Muğla Sıtkı Koçman University, Muğla, Turkey.
Mehmet
M
Öztürk
Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep, Turkey.
Ayşegül
A
Karaküçük-İyidoğan
Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
Miris
M
Dikmen
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, İstanbul, Turkey.
Bedia
B
Koçyiğit-Kaymakçıoğlu
Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep, Turkey. Electronic address: oruc@gantep.edu.tr.
Emine Elçin
EE
Oruç-Emre
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002091:Butyrylcholinesterase / Q000378:metabolism*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D062105:Molecular Docking Simulation; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D006835:Hydrazones; D010880:Piperidines; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
Anticholinesterase activity; Antioxidant activity; Hydrazone; Molecular docking; Piperidine