Abstract
Several novel isoquino[4,5-bc]acridine derivatives have been designed and synthesized. Their DNA-binding, anti-tumor and DNA-photo-damaging properties were investigated. A4 exhibited the highest anti-tumor activities against both A 549 (human lung cancer cell) and P388 (murine leukemia cells). All these compounds were found to be more cytotoxic against P388 than against A549. Under 365-nm light irradiation, A3 damaged plasmid DNA pBR322 at <2 microM and cleaved DNA from form I to 100% form II by 50 microM. The mechanism studies revealed that A3 damaged DNA by electron transfer mechanism and singlet oxygen species.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acridines / chemical synthesis
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Acridines / chemistry*
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Acridines / metabolism
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Acridines / pharmacology*
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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DNA Damage
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DNA, Neoplasm / drug effects*
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DNA, Neoplasm / metabolism
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Drug Design
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Humans
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Intercalating Agents / chemical synthesis
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Intercalating Agents / chemistry
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Intercalating Agents / metabolism
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Intercalating Agents / pharmacology
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Isoquinolines / chemical synthesis
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Isoquinolines / chemistry
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Isoquinolines / metabolism
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Isoquinolines / pharmacology
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Leukemia P388 / drug therapy
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Leukemia P388 / metabolism
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Mice
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Photobiology
Substances
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Acridines
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Antineoplastic Agents
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DNA, Neoplasm
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Intercalating Agents
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Isoquinolines