Fluorinated quinoid inhibitor: possible `pure' arylator predicted by the simple theoretical calculation

Ham, Seung Wook; Choe, Jong In; Wang, Meifang; Peyregne, Vincent; Carr, Brian I.

doi:10.1016/j.bmcl.2004.05.009

Cited by 29 publications

(6 citation statements)

References 27 publications

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“…In the case of 1,4-dimethoxy-2-methylnaphthalene, the absence of the quinone nucleus would block the ability of this molecule to participate in redox reactions [17]. In the case of pentafluoromenadione, the presence of the five fluorine atoms causes a large change in the behaviour of electrons (negative inductive effect) of the naphthoquinone nucleus; accordingly, the reduction potential of pentafluoromenadione would be in the order of 400 mV compared with −203 mV for menadione [18]. This reduction potential for the pentafluorinated analog of menadione would obviate redox function.…”

Section: Discussionmentioning

confidence: 99%

In vitro Activation of heme oxygenase-2 by menadione and its analogs

Vukomanovic

Rahman

Bilokin³

et al. 2014

Medical Gas Research

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BackgroundPreviously, we reported that menadione activated rat, native heme oxygenase-2 (HO-2) and human recombinant heme oxygenase-2 selectively; it did not activate spleen, microsomal heme oxygenase-1. The purpose of this study was to explore some structure–activity relationships of this activation and the idea that redox properties may be an important aspect of menadione efficacy.MethodsHeme oxygenase activity was determined in vitro using rat spleen and brain microsomes as the sources of heme oxygenase-1 and −2, respectively, as well as recombinant, human heme oxygenase-2.ResultsMenadione analogs with bulky aliphatic groups at position-3, namely vitamins K1 and K2, were not able to activate HO-2. In contrast, several compounds with similar bulky but less lipophilic moieties at position-2 (and −3) were able to activate HO-2 many fold; these compounds included polar, rigid, furan-containing naphthoquinones, furan-benzoxazine naphthoquinones, 2-(aminophenylphenyl)-3-piperidin-1-yl naphthoquinones. To explore the idea that redox properties might be involved in menadione efficacy, we tested analogs such as 1,4-dimethoxy-2-methylnaphthalene, pentafluoromenadione, monohalogenated naphthoquinones, α-tetralone and 1,4-naphthoquinone. All of these compounds were inactive except for 1,4-naphthoquinone. Menadione activated full-length recombinant human heme oxygenase-2 (FL-hHO-2) as effectively as rat brain enzyme, but it did not activate rat spleen heme oxygenase.ConclusionsThese observations are consistent with the idea that naphthoquinones such as menadione bind to a receptor in HO-2 and activate the enzyme through a mechanism that may involve redox properties.

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Section: Discussionmentioning

confidence: 99%

In vitro Activation of heme oxygenase-2 by menadione and its analogs

Vukomanovic

Rahman

Bilokin³

et al. 2014

Medical Gas Research

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“…ROS generation with naphthoquinones represents a challenge in the design of new active compounds, principally with anticancer effect. In this context, the addition/substitution on naphthoquinone moiety by atoms or groups such as flour, oxygen, or amine can be modulated by redox properties, decreasing the toxicity levels and maintaining or potentiating the biological effect [14,15,16]. Several quinones from natural origin, like β-laphachone and menadione, among others, have been well characterized by their specific selectivity for cell lines, responding to temporal curse and dose response.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

et al. 2019

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We performed an extensive analysis about the reaction conditions of the 1,4-Michael addition of amino acids to 1,4-naphthoquinone and substitution to 2,3-dichloronaphthoquinone, and a complete evaluation of stoichiometry, use of different bases, and the pH influence was performed. We were able to show that microwave-assisted synthesis is the best method for the synthesis of naphthoquinone–amino acid and chloride–naphthoquinone–amino acid derivatives with 79–91% and 78–91% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone–amino acid derivatives mainly display one quasi-reversible redox reaction process. Interestingly, it was shown that naphthoquinone derivatives possess a selective antitumorigenic activity against cervix cancer cell lines and chloride–naphthoquinone–amino acid derivatives against breast cancer cell lines. Furthermore, the newly synthetized compounds with asparagine–naphthoquinones (3e and 4e) inhibited ~85% of SiHa cell proliferation. These results show promising compounds for specific cervical and breast cancer treatment.

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“…Similarly, for converting the stable CF 3 group, Yoshida's group [88] developed a boron tribromide-mediated Friedel-Crafts-type acylation of arenes with benzotrifluoride (Scheme 31). Through the three-times defluorobromination of benzotrifluoride to generate the tribromide, then reacted with methanol and arene, various diaryl ketones (176)(177)(178) and aromatic esters (179)(180)(181)(182) were synthesized. This protocol provided an alternative method for the formation of diaryl ketone.…”

Section: Benzylic and Allylic C-f Bonds Cleavagementioning

confidence: 99%

“…As its known, 1,4-naphthoquinone derivatives have properties of antioxidant, anti-malarial and so on [177]. Polyfluorinated functionalized 1,4-naphthoquinones could act as inhibitors for the growth of cancer cells [178]. Moreover, 1,4-benzoquinone derivatives exhibit diverse biological activity as well.…”

Section: Other Modes Promote Defluorinative Amination/ Azidationmentioning

confidence: 99%

C-F bond activation under transition-metal-free conditions

Song

et al. 2021

Sci. China Chem.

108

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The unique properties of fluorine-containing organic compounds make fluorine substitution attractive for the development of pharmaceuticals and various specialty materials, which have inspired the evolution of diverse C-F bond activation techniques. Although many advances have been made in functionalizations of activated C-F bonds utilizing transition metal complexes, there are fewer approaches available for nonactivated C-F bonds due to the difficulty in oxidative addition of transition metals to the inert C-F bonds. In this regard, using Lewis acid to abstract the fluoride and light/radical initiator to generate the radical intermediate have emerged as powerful tools for activating those inert C-F bonds. Meanwhile, these transition-metal-free processes are greener, economical, and for the pharmaceutical industry, without heavy metal residues. This review provides an overview of recent C-F bond activations and functionalizations under transition-metal-free conditions. The key mechanisms involved are demonstrated and discussed in detail. Finally, a brief discussion on the existing limitations of this field and our perspective are presented.

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Fluorinated quinoid inhibitor: possible `pure' arylator predicted by the simple theoretical calculation

Cited by 29 publications

References 27 publications

In vitro Activation of heme oxygenase-2 by menadione and its analogs

In vitro Activation of heme oxygenase-2 by menadione and its analogs

Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

C-F bond activation under transition-metal-free conditions

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