New 2-Acetyl-3-aminophenyl-1,4-naphthoquinones: Synthesis andIn VitroAntiproliferative Activities on Breast and Prostate Human Cancer Cells

Abstract

The reaction of 2-acyl-1,4-naphthoquinones with N,N-dimethylaniline and 2,5-dimethoxyaniline, promoted by catalytic amounts of CeCl3·7H2O under “open-flask” conditions, produced a variety of 2-acyl-3-aminophenyl-1,4-naphthoquinones structurally related to the cytotoxic 2-acetyl-3-phenyl-1,4-naphthoquinone, an inhibitor of the heat shock chaperone protein Hsp90. The members of the 2-acyl-3-aminophenyl-1,4-naphthoquinone series were isolated in good yields (63-98%). The cyclic voltammograms of the 2-acyl-3-aminophenyl-1,4-naphthoquinone exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasireversible oxidation peaks. The first and second half-wave potential values (E1/2) of the members of the series are sensitive to the push-pull electronic effects of the substituents in the naphthoquinone scaffold. Furthermore, the in vitro antiproliferative properties of these new quinones were evaluated on two human cancer cells DU-145 (prostate) and MCF-7 (mammary) and a nontumorigenic HEK-293 (kidney) cell line, using the MTT colorimetric method. Two members, within the series, exhibited interesting cytotoxic activities on human prostate and mammary cancer cells.

Discovery of New 2-Phenylamino-3-Acyl-1,4-Naphthoquinones as Inhibitors of Cancer Cells Proliferation. Searching for Intra-cellular Targets Playing a Role in Cancer Cells Survival

“…In agreement with other research groups, we support the hypothesis that a pro-oxidant treatment contributes, in a substantive way, to the elimination of cancer cells, via the induction of an oxidative stress leading to different manners of cell demise [ 18 22]. In this context, we have synthesized several quinone compounds and their biological activities have been assessed on a variety of human cancer cells [23][24][25][26][27][28][29].…”

“…The products required for the cytotoxic evaluation were synthesized according to our previously reported three-step procedure [9,29]. They included a) solar photoacylation Friedel-Crafts reaction of 1,4-naphthoquinone (NQ) with aldehydes [56]; b) oxidation of the resulting acylnaphthohydroquinones (2-acylNQ) with Ag2O to give the 2-phenylamino-1,4-naphtoquinones (AcylNQ), and c) oxidative amination reaction of the products resulting in the previous step, with phenylamine, to produce the respective 2-phenylamino-3-acyl-1,4-naphtoquinones 1-14 (Scheme 1).…”

On the Reaction of 2-Alkanoylnaphthohydroquinones with Hydroxylamine: Access to Cytotoxic 2-(Hydroxyamino)-1,4-naphthoquinone and Their 3-(Hydroxyimino)alkyl Analogous

“…Aluminum foil 60F 254 was used for analytical thin layer chromatography. The acylbenzohydroquinones (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) were prepared according to a previously reported procedure [12].…”

“…2-Acylated-1,4-benzo-and 1,4-naphthohydroquinones I and III (Figure 1) are of current interest by their use as synthetic building blocks for carbo-and heterocyclic compounds endowed with cytotoxic and antiproliferative effects in various human cancer cells, as well as antifungal activities [1][2][3][4][5][6][7][8]. The synthetic advantage of these acylhydroquinones [9][10][11][12][13][14] emerges from the coexistence of the hydroquinone and the ortho-hydroxyacylarene fragments in their structures.…”

“…In previous studies performed in our laboratory, two series of cytotoxic active acyl-containing quinoid compounds, V and VI, were prepared from acetylhydroquinones types I and III (R � alkyl and aryl) [3,4]. An interesting possibility to improve the cytotoxic activities of this series is to replace the corresponding acyl substituents with their oximes.…”