Tumor Cell Toxicity of Hypericin and Related Analogs¶

Wills, Nick J.; Park, Jaehun; Wen, Jia; Kesavan, Sarathy; Kraus, George A.; Petrich, Jacob W.; Carpenter, Susan

doi:10.1562/0031-8655(2001)0740216tctoha2.0.co2

Cited by 6 publications

(8 citation statements)

References 23 publications

(28 reference statements)

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“…The mechanism currently thought to be responsible for the toxicity of hypericin involves the production of singlet oxygen and superoxide radicals upon light-activation [4,[28][29][30]. The production of ROS by hypericin upon light activation can cause oxidative damage leading to cell death [4,[28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

Schmitt

Liu

Murphy

et al. 2006

Journal of Photochemistry and Photobiology B: Biology

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Clinical evidence suggests that administration of Hypericum perforatum (Hp) extracts containing the photo-activated hypericin compounds may cause fewer skin photosensitization reactions than administration of pure hypericin. This study was conducted to determine whether the phototoxicity of hypericin in HaCaT keratinocytes could be attenuated by H. perforatum extracts and constituents. Two extracts, when supplemented with 20 μM hypericin: (1) an ethanol re-extraction of residue following a chloroform extraction (denoted ethanol(-chloroform)) (3.35 μM hypericin and 124.0 μM total flavonoids); and (2) a chloroform extract (hypericin and flavonoids not detected), showed 25% and 50% (p < 0.0001) less phototoxicity than 20 μM hypericin alone. Two H. perforatum constituents, when supplemented with 20 μM hypericin: (1) 10 μM chlorogenic acid; and (2) 0.25 μM pyropheophorbide, exhibited 24% (p < 0.05) and 40% (p < 0.05) less phototoxicity than 20 μM hypericin alone. The peroxidation of arachidonic acid was assessed as a measure of oxidative damage by photo-activated hypericin, but this parameter of lipid peroxidation was not influenced by the extracts or constituents. However α-tocopherol, a known antioxidant also did not influence the amount of lipid peroxidation induced in this system. These observations indicate that hypericin combined with H. perforatum extracts or constituents may exert less phototoxicity than pure hypericin, but possibly not through a reduction in arachidonic acid peroxidation.

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Section: Discussionmentioning

confidence: 99%

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

Schmitt

Liu

Murphy

et al. 2006

Journal of Photochemistry and Photobiology B: Biology

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“…Of course, part of the difference in activity may also be attributed to the ability of the quinones to solubilize themselves in the viral membrane. Factors such as this have been discussed in detail elsewhere (76).…”

Section: Resultsmentioning

confidence: 97%

Synthesis of Hydroxy and Methoxy Perylene Quinones, Their Spectroscopic and Computational Characterization, and Their Antiviral Activity^¶

Krishnamoorthy¹,

Webb²,

Nguyen³

et al. 2005

Photochem & Photobiology

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Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light‐induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the “bay region.” The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (∼450–800 nm) and relatively more intense and narrow features at wavelengths ≤350 nm. High‐level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from So to S2 and to higher‐lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest‐energy trans methoxy ground state isomer and the lowest‐energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light‐induced antiviral activity to each other, but significantly less than that of hypericin.

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“…1b), which affords pseudohypericin a “handle” for the tethering of luciferin, is absent on hypericin and may contribute to the reduced antiviral activity of pseudohypericin as compared with hypericin. The factors contributing to the relative antiviral and antitumor activities of photoactive compounds are rather complicated to assess, as indicated in two recent articles dealing with cytotoxicity (23,24). In particular, a proper comparison of a series of such analogs must carefully consider their (1) association with the target; (2) absorption spectrum; and (3) excited‐state photochemistry (24).…”

Section: Resultsmentioning

confidence: 99%

“…The factors contributing to the relative antiviral and antitumor activities of photoactive compounds are rather complicated to assess, as indicated in two recent articles dealing with cytotoxicity (23,24). In particular, a proper comparison of a series of such analogs must carefully consider their (1) association with the target; (2) absorption spectrum; and (3) excited‐state photochemistry (24). It has been proposed that this lower activity can be attributed to the lower extinction coefficient of pseudohypericin with respect to that of hypericin (24).…”

Section: Resultsmentioning

confidence: 99%

“…In particular, a proper comparison of a series of such analogs must carefully consider their (1) association with the target; (2) absorption spectrum; and (3) excited‐state photochemistry (24). It has been proposed that this lower activity can be attributed to the lower extinction coefficient of pseudohypericin with respect to that of hypericin (24).…”

Section: Resultsmentioning

confidence: 99%

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Toward the Molecular Flashlight: Preparation, Properties, and Photophysics of a Hypericin-luciferin Tethered Molecule¶

Wen

Chowdhury

Wills

et al. 2007

Photochemistry and Photobiology

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The synthesis of a molecule containing hypericin and luciferin moieties joined by a tether is reported. The light‐induced (in vitro) antiviral activity as well as the photophysical properties of this new compound are measured and compared with those of the parent compounds, hypericin and pseudohypericin. This tethered molecule exhibits excited‐state behavior that is very similar to that of its parent compounds and antiviral activity that is identical, within experimental error, to that of its more closely related parent compound, pseudohypericin. The implications for a photodynamic therapy that is independent of external light sources are discussed.

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Tumor Cell Toxicity of Hypericin and Related Analogs¶

Cited by 6 publications

References 23 publications

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

Synthesis of Hydroxy and Methoxy Perylene Quinones, Their Spectroscopic and Computational Characterization, and Their Antiviral Activity^¶

Toward the Molecular Flashlight: Preparation, Properties, and Photophysics of a Hypericin-luciferin Tethered Molecule¶

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Tumor Cell Toxicity of Hypericin and Related Analogs¶

Cited by 6 publications

References 23 publications

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

Synthesis of Hydroxy and Methoxy Perylene Quinones, Their Spectroscopic and Computational Characterization, and Their Antiviral Activity¶

Toward the Molecular Flashlight: Preparation, Properties, and Photophysics of a Hypericin-luciferin Tethered Molecule¶

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Product

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Synthesis of Hydroxy and Methoxy Perylene Quinones, Their Spectroscopic and Computational Characterization, and Their Antiviral Activity^¶