Abstract
A series of N-mustards, which was conjugated to mono- or bis-naphthalimides with a flexible amine link, were synthesized and evaluated for cytotoxicity against five cancer cell lines (HCT-116, PC-3, U87 MG, Hep G2 and SK-OV-3). Several compounds displayed better activities than the control compound amonafide. Further evaluations by fluorescence spectroscopy studies and DNA-interstrand cross-linking assays revealed that the derivatives showed both alkylating and intercalating properties. Among the derivatives, the bis-naphthalimide N-mustard derivative 11b was found to exhibit the highest cytotoxic activity and DNA cross-linking ability. Both 11b and 7b induce HCT-116 cell apoptosis by S phase arrest.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Alkylating / chemical synthesis*
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Antineoplastic Agents, Alkylating / pharmacology
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Apoptosis / drug effects
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Cell Cycle Checkpoints / drug effects
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Drug Screening Assays, Antitumor
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HCT116 Cells
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Hep G2 Cells
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Humans
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Inhibitory Concentration 50
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Naphthalimides / chemical synthesis*
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Naphthalimides / pharmacology
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Phosphoramide Mustards / chemical synthesis*
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Phosphoramide Mustards / pharmacology
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases / metabolism
Substances
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Antineoplastic Agents, Alkylating
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Naphthalimides
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Phosphoramide Mustards
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PARP1 protein, human
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases