Abstract
In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC₅₀ values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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DNA Damage
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Furocoumarins / chemical synthesis
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Furocoumarins / chemistry
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Furocoumarins / pharmacology
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Humans
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Membrane Potential, Mitochondrial / drug effects
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Phosphatidylserines / metabolism
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Photosensitizing Agents / chemical synthesis*
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Photosensitizing Agents / chemistry
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Photosensitizing Agents / toxicity
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Pyrroles / chemical synthesis
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Pyrroles / chemistry*
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Pyrroles / toxicity
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / toxicity
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Reactive Oxygen Species / metabolism
Substances
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Furocoumarins
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Phosphatidylserines
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Photosensitizing Agents
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Pyrroles
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Quinolines
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Reactive Oxygen Species
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pyrroloquinoline
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angelicin