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 center dot(+)) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compound3dshowed the better result with 51.52% of antioxidant activity at 1 mg/mL, while in ABTS center dot(+)was2e(47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products2a,2c, and2eagainst cervix line HeLa, with 50% growth inhibition (GI(50)) of 5.6, 15.0, and 17.0 mu M, 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 was2ewith a 50% inhibitory concentration (IC50) of 0.0586 mM, followed by2a(0.0902 mM). No inhibition in the evaluated concentrations was observed for products2dand3a-d. Docking of2aand2ewas 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, specially2aand2e, could be further derivatized in the search for new and improved drugs.