Antioxidant, antiproliferative, and acetylcholinesterase inhibition activity of amino alcohol derivatives from 1,4-naphthoquinone

Natural and synthetic naphthoquinones have demonstrated numerous biological activities; therefore, they provide an interesting scaffold for medicinal chemists in the search for new drugs. A series of amino alcohol derivatives from 1,4-naphthoquinone with a free (2a–e) and acetylated (3a–d) hydroxyl group were synthesized, characterized, and evaluated as antioxidant agents employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compound 3d showed the better result with 51.52% of antioxidant activity at 1 mg/mL, while in ABTS·+ was 2e (47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products 2a, 2c, and 2e against cervix line HeLa, with 50% growth inhibition (GI50) of 5.6, 15.0, and 17.0 μM, respectively. All synthesized compounds presented varying degrees of response, some of them with similar results compared with the positive control 5-fluorouracil. AChE inhibition of the products was not as strong as the positive control galantamine; the most potent compound was 2e with a 50% inhibitory concentration (IC50) of 0.0586 mM, followed by 2a (0.0902 mM). No inhibition in the evaluated concentrations was observed for products 2d and 3a-d. Docking of 2a and 2e was realized against AChE in order to gain insight into the interactions made between them and the enzyme residues in its catalytic gorge. In silico calculations for all synthesized products showed their drug-like properties. Alcohol derivatives, specially 2a and 2e, could be further derivatized in the search for new and improved drugs.