Near-Visible Light Generation of a Quinone Methide from 3-Hydroxymethyl-2-anthrol

Škalamera, Đani; Mlinarić‐Majerski, Kata; Martin-Kleiner, Irena; Kralj, Marijeta; Wan, Peter; Basarić, Nikola

doi:10.1021/jo500290y

Cited by 22 publications

(50 citation statements)

References 66 publications

(79 reference statements)

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“…After cooling to room temp., Et 2 O (20 mL) was added, and the reaction mixture was filtered through a sintered glass funnel. [86] Results are compiled in the Supporting Information. The residue was purified by chromatography on a silica gel column (Et 2 O/hexane, 1:1) to afford pure 13Me (6 mg, 3 %) as colorless crystals; m.p.…”

Section: Methyl 2-cyanoadamantane-1-carbamate (13me)mentioning

confidence: 99%

Photodecarboxylation of Adamantane Amino Acids Activated by Phthalimide

et al. 2016

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Adamantane α‐, β‐, and δ‐amino acids activated by phthalimide (i.e., 3–6) were synthesized, and their photochemical reactivities were investigated. Amino acid derivatives 3–6 underwent a photoinduced electron transfer (PET) and decarboxylation reaction sequence, most probably through a triplet excited state. The decarboxylations of the β‐amino acid derivatives were succeeded by cyclization reactions that afforded complex polycyclic molecules with potential biological interest. The adamantyl radical that is produced by the photoinduced decarboxylation could be trapped by alkenes or oxygen to deliver adducts or alcohols, respectively. The photodecarboxylation process was shown to be more efficient under acetone sensitization conditions (with quantum yields, Φ = 0.02–0.5) than upon direct excitation, and the reactivity was dependent on the chain length (intramolecular distance) between the electron donor (carboxylate) and acceptor (phthalimide in the triplet excited state) of the derivative. The formation of different radicals, that is, the 1‐ or 2‐adamantyl intermediate, probably does not affect the overall rate of the decarboxylation This current report provides a better understanding of photodecarboxylation and the rational design of molecular systems to undergo photoinduced decarboxylation and cyclization reactions.

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Section: Methyl 2-cyanoadamantane-1-carbamate (13me)mentioning

confidence: 99%

Photodecarboxylation of Adamantane Amino Acids Activated by Phthalimide

et al. 2016

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“…21 Characterization of product 23 compares well with literature (mp = 160-163°C). (24) was prepared in a Grignard reaction from 3-bromo-4'-methoxybiphenyl and 2-adamantanone in 78 % yield according to the published procedure. 21 Characterization of product 24 compares well with literature (mp = 103-105°C).…”

Section: Research Articlementioning

confidence: 99%

“…18 We became interested in the photochemical generation of QMs with sterically congested lipophylic substituents 19,20 and their antiproliferative activities. [21][22][23][24] A series of simple phenols, 19 biphenyls, [20][21][22] naphthols, 23 and anthrols 24 were synthesized and their antiproliferative activities were investigated. Since compounds that generate QMs are known b-lactamase inhibitors, 18 we were also prompted to investigate their antimicrobic activities.…”

Section: Introductionmentioning

confidence: 99%

In vitro investigation of the antimicrobial activity of a series of lipophilic phenols and naphthols

Govender¹,

Govinden²,

Mocktar³

et al. 2016

S.Afr.j.chem.

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Five groups of phenols/naphthols (42 compounds in total) were synthesized and screened against Gram-positive Staphylococcus aureus and Bacillus subtilis, Gram-negative Escherichia coli and Klebsiella pneumoniae, and the fungus Candida albicans. Whereas compounds were found inactive against Gram-negative bacteria, potent activities against Gram-positive bacteria were observed. The activities correlate with the ability of molecules to form quinone methides, suggesting potential new modes of action.

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“…Although dehydration takes place less efficiently then the elimination of ammonium salts, it is more appealing due to the fact that the thermal back-hydration regenerates the starting material, so there is no loss of an active molecule inside the cell due to the competing reaction of a QM with H 2 O. In addition to simple phenol derivatives [23], the photodehydration has been demonstrated on naphthols [24], or anthrol derivatives [25,26]. Adequately substituted anthrols 1 can be excited with near visible light at λ > 400 nm delivering QM1 in photodehydration or photodeamination [26].…”

mentioning

confidence: 99%

“…The QMs react with nucleophiles giving adducts. Preliminary biological investigation indicated enhancement of antiproliferative activity for the human cancer cells which were irradiated, suggesting that the effect is due to intracellular photochemical formation of QMs [25,26].…”

mentioning

confidence: 99%

Selective photocytotoxicity of anthrols on cancer stem-like cells: The effect of quinone methides or reactive oxygen species

Uzelac

Škalamera

Mlinarić‐Majerski

et al. 2017

European Journal of Medicinal Chemistry

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Cancer stem cells (CSCs) are a subpopulation of cancer cells that share properties of embryonic stem cells like pluripotency and self-renewal and show increased resistance to chemo- and radiotherapy. Targeting CSC, rather than cancer cells in general, is a novel and promising strategy for cancer treatment. Novel therapeutic approaches, such as photodynamic therapy (PDT) have been investigated. A promising group of phototherapeutic agents are reactive intermediates - quinone methides (QMs). This study describes preparation of QM precursor, 2-hydroxy-3-hydroxymethylanthracene (2) and a detailed photochemical and photobiological investigation on similar anthracene derivatives 3 and 4. Upon photoexcitation with near visible light at λ > 400 nm 1 and 2 give QMs, that were detected by laser flash photolysis and their reactivity with nucleophiles has been demonstrated in the preparative irradiation experiments where the corresponding adducts were isolated and characterized. 3 and 4 cannot undergo photodehydration and deliver QM, but lead to the formation of phenoxyl radical and singlet oxygen, respectively. The activity of 1-4 was tested on a panel of human tumor cell lines, while special attention was devoted to demonstrate their potential selectivity towards the cells with CSC-like properties (HMLEshEcad). Upon the irradiation of cell lines treated with 1-4, an enhancement of antiproliferative activity was demonstrated, but the DNA was not the target molecule. Confocal microscopy revealed that these compounds entered the cell and, upon irradiation, reacted with cellular membranes. Our experiments demonstrated moderate selectivity of 2 and 4 towards CSC-like cells, while necrosis was shown to be a dominant cell death mechanism. Especially interesting was the selectivity of 4 that produced higher levels of ROS in CSC-like cells, which forms the basis for further research on cancer phototherapy, as well as for the elucidation of the underlying mechanism of the observed CSC selectivity based on oxidative stress activation.

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Near-Visible Light Generation of a Quinone Methide from 3-Hydroxymethyl-2-anthrol

Cited by 22 publications

References 66 publications

Photodecarboxylation of Adamantane Amino Acids Activated by Phthalimide

Photodecarboxylation of Adamantane Amino Acids Activated by Phthalimide

In vitro investigation of the antimicrobial activity of a series of lipophilic phenols and naphthols

Selective photocytotoxicity of anthrols on cancer stem-like cells: The effect of quinone methides or reactive oxygen species

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