Half-Wave Potentials and In Vitro Cytotoxic Evaluation of 3-Acylated 2,5-Bis(phenylamino)-1,4-benzoquinones on Cancer Cells

Abstract

A broad range of 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones were synthesized and their voltammetric values, as well as in vitro cancer cell cytotoxicities, were assessed. The members of this series were prepared from acylbenzoquinones and phenylamines, in moderate to good yields (47–74%), through a procedure involving a sequence of two in situ regioselective oxidative amination reactions. The cyclic voltammograms of the aminoquinones exhibit two one-electron reduction waves to the corresponding radical-anion and dianion, and two quasi-reversible oxidation peaks. The first and second half-wave potential values (E1/2) of the members of the series were sensitive to the push-pull electronic effects of the substituents around the benzoquinone nucleus. The in vitro cytotoxic activities of the 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones against human cancer cells (bladder and prostate) and non-tumor human embryonic kidney cells were measured using the MTT colorimetric method. The substitution of both aniline groups, by either methoxy (electron donating effect) or fluorine (electron withdrawal effect), decreased the cytotoxicity in the aminoquinones. Among the members of the unsubstituted phenylamino series, two of the 18 compounds showed interesting anti-cancer activities. A preliminary assay, looking for changes in the expression of selected genes, was performed. In this context, the two compounds increased TNF gene expression, suggesting an association with an inflammatory-like response.

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].…”

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.…”

Green Synthesis and Electrochemical Properties of Mono- and Dimers Derived from Phenylaminoisoquinolinequinones

“…A common aminoquinoid unit appeared as a key structural scaffold in diverse natural occurring cytotoxic compounds, such as smenospongine [16,17], streptonigrin [18,19,20,21,22,23], mansouramicyn C [24,25] and, synthetic cytotoxic 1,4-benzoquinones, 1,4-naphthoquinones [26,27], and heterocyclic analogs [28,29,30,31,32].…”