Abstract
The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4- to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines (MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3 and 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed, and a nuclear distribution pattern was observed for 4, which contains a nuclear localization signaling sequence.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Biological Transport
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Cell Line, Tumor
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Coumarins / chemical synthesis
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Coumarins / chemistry*
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Coumarins / metabolism*
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Coumarins / pharmacology
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DNA Topoisomerases, Type I / metabolism
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Dendrimers / chemistry*
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Green Fluorescent Proteins / metabolism
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Heterocyclic Compounds, 4 or More Rings / chemical synthesis
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Heterocyclic Compounds, 4 or More Rings / chemistry*
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Heterocyclic Compounds, 4 or More Rings / metabolism*
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Humans
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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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Nuclear Localization Signals / chemistry*
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Polyethylene Glycols / chemistry
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Transfection
Substances
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Antineoplastic Agents
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Coumarins
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Dendrimers
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Heterocyclic Compounds, 4 or More Rings
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Isoquinolines
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Nuclear Localization Signals
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lamellarin D
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Green Fluorescent Proteins
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Polyethylene Glycols
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DNA Topoisomerases, Type I