Antioxidant, antiproliferative, and acetylcholinesterase inhibition activity of amino alcohol derivatives from 1,4-napht
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Medicinal Chemistry Research https://doi.org/10.1007/s00044-020-02617-1
ORIGINAL RESEARCH
Antioxidant, antiproliferative, and acetylcholinesterase inhibition activity of amino alcohol derivatives from 1,4-naphthoquinone Arturo Estolano-Cobián1 Eduardo Noriega-Iribe1 Laura Díaz-Rubio1 José M. Padrón2 Mirna Brito-Perea1 José Manuel Cornejo-Bravo1 Daniel Chávez3 Raúl Romero Rivera1 Juan Manuel Quintana-Melgoza1 J. Cruz-Reyes1 Iván Córdova-Guerrero 1 ●
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Received: 2 July 2020 / Accepted: 13 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 1,4naphthoquinone 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. Keywords Naphthoquinone Amino alcohol Antioxidant Antiproliferative Acetylcholinesterase inhibition Docking ●
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Introduction
Supplementary information The online version of this article (https:// doi.org/10.1007/s00044-020-02617-1) contains supplementary material, which is available to authorized users. * Iván Córdova-Guerrero [email protected] 1
Facultad de Ciencias Químicas e Ingeniería, Universidad Autónoma de Baja California, 22390 Tijuana, B.C., Mexico
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BioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain
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Centro de Graduados
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