Sterically Congested Adamantylnaphthalene Quinone Methides

Five new (2-adamantyl)­naphthol derivatives (<b>5</b>–<b>9</b>, quinone methide precursors, <b>QMP</b>) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of <b>QMP 5</b> to S₁ leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide <b>QM5</b> which was characterized by LFP (in CH₃CN–H₂O, λ_max = 370 nm, τ = 0.19 ms). On irradiation of <b>QMP 5</b> in CH₃OH–H₂O (4:1), the quantum yield of methanolysis is <i>Φ =</i> 0.70. Excitation of naphthols <b>QMP 6</b>–<b>8</b> to S₁ in CH₃CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, <b>QMP 6</b>–<b>8</b> undergo solvent-assisted PT giving <b>QM6</b> or zwitterion <b>QM8</b> that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. <b>QMP 9</b> in a protic solvent undergoes two competitive processes, photosolvolysis via <b>QM9</b> and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. <b>QM9</b> has been characterized by LFP (in CH₃CN–H₂O, λ_max > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, <b>QM10</b> and <b>QM11</b> were synthesized thermally and characterized by X-ray crystallography. <b>QM10</b> and <b>QM11</b> do not react with H₂O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of <b>5</b>–<b>9</b> was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with <b>5</b> to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of <b>QM5</b>

Sterically Congested Adamantylnaphthalene Quinone Methides

Five new (2-adamantyl)­naphthol derivatives (<b>5</b>–<b>9</b>, quinone methide precursors, <b>QMP</b>) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of <b>QMP 5</b> to S₁ leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide <b>QM5</b> which was characterized by LFP (in CH₃CN–H₂O, λ_max = 370 nm, τ = 0.19 ms). On irradiation of <b>QMP 5</b> in CH₃OH–H₂O (4:1), the quantum yield of methanolysis is <i>Φ =</i> 0.70. Excitation of naphthols <b>QMP 6</b>–<b>8</b> to S₁ in CH₃CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, <b>QMP 6</b>–<b>8</b> undergo solvent-assisted PT giving <b>QM6</b> or zwitterion <b>QM8</b> that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. <b>QMP 9</b> in a protic solvent undergoes two competitive processes, photosolvolysis via <b>QM9</b> and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. <b>QM9</b> has been characterized by LFP (in CH₃CN–H₂O, λ_max > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, <b>QM10</b> and <b>QM11</b> were synthesized thermally and characterized by X-ray crystallography. <b>QM10</b> and <b>QM11</b> do not react with H₂O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of <b>5</b>–<b>9</b> was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with <b>5</b> to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of <b>QM5</b>

Sterically Congested Adamantylnaphthalene Quinone Methides

Five new (2-adamantyl)­naphthol derivatives (<b>5</b>–<b>9</b>, quinone methide precursors, <b>QMP</b>) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of <b>QMP 5</b> to S₁ leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide <b>QM5</b> which was characterized by LFP (in CH₃CN–H₂O, λ_max = 370 nm, τ = 0.19 ms). On irradiation of <b>QMP 5</b> in CH₃OH–H₂O (4:1), the quantum yield of methanolysis is <i>Φ =</i> 0.70. Excitation of naphthols <b>QMP 6</b>–<b>8</b> to S₁ in CH₃CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, <b>QMP 6</b>–<b>8</b> undergo solvent-assisted PT giving <b>QM6</b> or zwitterion <b>QM8</b> that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. <b>QMP 9</b> in a protic solvent undergoes two competitive processes, photosolvolysis via <b>QM9</b> and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. <b>QM9</b> has been characterized by LFP (in CH₃CN–H₂O, λ_max > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, <b>QM10</b> and <b>QM11</b> were synthesized thermally and characterized by X-ray crystallography. <b>QM10</b> and <b>QM11</b> do not react with H₂O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of <b>5</b>–<b>9</b> was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with <b>5</b> to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of <b>QM5</b>

Sterically Congested Adamantylnaphthalene Quinone Methides

Five new (2-adamantyl)­naphthol derivatives (<b>5</b>–<b>9</b>, quinone methide precursors, <b>QMP</b>) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of <b>QMP 5</b> to S₁ leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide <b>QM5</b> which was characterized by LFP (in CH₃CN–H₂O, λ_max = 370 nm, τ = 0.19 ms). On irradiation of <b>QMP 5</b> in CH₃OH–H₂O (4:1), the quantum yield of methanolysis is <i>Φ =</i> 0.70. Excitation of naphthols <b>QMP 6</b>–<b>8</b> to S₁ in CH₃CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, <b>QMP 6</b>–<b>8</b> undergo solvent-assisted PT giving <b>QM6</b> or zwitterion <b>QM8</b> that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. <b>QMP 9</b> in a protic solvent undergoes two competitive processes, photosolvolysis via <b>QM9</b> and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. <b>QM9</b> has been characterized by LFP (in CH₃CN–H₂O, λ_max > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, <b>QM10</b> and <b>QM11</b> were synthesized thermally and characterized by X-ray crystallography. <b>QM10</b> and <b>QM11</b> do not react with H₂O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of <b>5</b>–<b>9</b> was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with <b>5</b> to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of <b>QM5</b>

Novel Substituted Benzothiophene and Thienothiophene Carboxanilides and Quinolones: Synthesis, Photochemical Synthesis, DNA-Binding Properties, Antitumor Evaluation and 3D-Derived QSAR Analysis

A series of new <i>N</i>,<i>N</i>-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo­[<i>b</i>]­thienyl- and thieno­[2,3-<i>b</i>]­thienylcarboxanilides and benzo­[<i>b</i>]­thieno­[2,3-<i>c</i>]- and thieno­[3′,2′:4,5]­thieno­[2,3-<i>c</i>]­quinolones were prepared. Quinolones were prepared by the reaction of photochemical dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives showed very prominent activity. By use of the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Higly predicitive 3D-derived QSAR models were obtained, and molecular properties that have the highest impact on antitumor activity were identified. Carboxanilides <b>6a</b>–<b>c</b> and quinolones <b>9a</b>–<b>c</b> and <b>11a</b> were evaluated for DNA binding propensities and topoisomerases I and II inhibition as part of their mechanism of action assessment. The evaluated differences in the mode of action nicely correlate with the results of the 3D-QSAR analysis. Taken together, the results indicate which modifications of the compounds from the series should further improve their anticancer properties