Novel fluorine-containing chiral hydrazide-hydrazones: Design, synthesis, structural elucidation, antioxidant and anticholinesterase activity, and in silico studies.

In this study, a series of fluorine-containing chiral hydrazide-hydrazone derivatives [III-XII] from ʟ-cysteine ethyl ester hydrochloride was synthesized as new antioxidant and anticholinesterase agents. The antioxidant activity of these derivatives was evaluated by ABTS+· and DPPH· scavenging and CUPRAC assays and the anticholinesterase activity by the Ellman method spectrophotometrically. The results of the antioxidant assay showed that compounds V, IX, and X exhibited higher activity than BHT and α-tocopherol used as positive standards. Among the synthesized derivatives, compound IX (IC50 : 2.3 ± 1.6 µM) exhibited higher acetylcholinesterase inhibitory activity than galantamine (IC50 : 4.5 ± 0.8 µM). Compounds XI (IC50 : 9.6 ± 1.0 µM), IX (IC50 : 12.5 ± 1.6 µM), III (IC50 : 16.0 ± 1.6 µM), X (IC50 : 17.2 ± 1.8 µM), VI (IC50 : 20.2 ± 0.8 µM), XII (IC50 : 21.5 ± 1.0 µM), and VII (IC50 : 24.6 ± 0.6 µM) displayed better butyrylcholinesterase inhibitory activity than galantamine (IC50 : 46.03 ± 0.14 µM). ADME-Tox analysis was used to probe the drug-like properties of the compounds. Molecular docking studies were also applied to understand the interactions between compounds and targets. The docking calculations were supported by the experimental data. In particular, compound IX, having better activity than galantamine against acetylcholinesterase and butyrylcholinesterase enzymes, was visualized using molecular docking.

Synthesis of novel chiral metal complexes derived from chiral thiosemicarbazide ligands as potential antioxidant agents.

Two new chiral thiosemicarbazide ligands and their Cu (II), Ni (II), Pd (II), and Zn (II) complexes were synthesized and characterized by nuclear magnetic resonance (NMR) (only for ligand), Fourier transform infrared (FT-IR), ultraviolet visible (UV-Vis), mass, and elemental analysis. The antioxidant activity of ligands and their metal complexes was examined. It was found that the antioxidant activity of metal complexes was better than their ligands. In addition, the antioxidant activity, as reflected by free radical scavenging, was evaluated. Besides, Pd (II) complexes exhibited better antioxidant activity than Ni (II), Cu (II), and Zn (II) complexes. Therefore, complexes (3a-Pd and 3b-Pd) can be used as an antioxidant agent or antioxidant test standard.

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.