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

AbstractNatural 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, compound3d showed the better result with 51.52% of antioxidant activity at 1  mg/mL, while in ABTS·+ was2e (47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products2a,2c, and2e 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 was2e with a 50% inhibitory concentration (IC50) of 0.0586  mM, followed by2a (0.0902  mM). No inhibition in the evaluated concentrations was observed for products2d and3a-d. Docking of2a and2e was realized against AChE in order to gain insight into the i...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research