Abstract
A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC(50) = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC(50) = 3.93 μM), and significantly induced cell cycle arrest in G2/M phase. In addition, compound 22b could inhibit the tumor growth in colon nude mouse xenograft tumor model significantly and seemed safer than CA-4 when achieving a similar tumor suppression. This study provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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 / pharmacology*
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Antineoplastic Agents / toxicity
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Cell Cycle / drug effects
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Cell Line, Tumor
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Chemistry Techniques, Synthetic
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Female
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Humans
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Inhibitory Concentration 50
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Mice
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Mice, Inbred BALB C
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Models, Molecular
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Naphthalenes / chemical synthesis*
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Naphthalenes / chemistry
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Naphthalenes / pharmacology*
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Naphthalenes / toxicity
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Protein Multimerization / drug effects
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Protein Structure, Quaternary
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Tubulin / chemistry
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Tubulin Modulators / chemical synthesis*
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Tubulin Modulators / chemistry
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Tubulin Modulators / pharmacology*
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Tubulin Modulators / toxicity
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Xenograft Model Antitumor Assays
Substances
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1,3-bis(benzylidene)-3,4-dihydro-1H-naphthalen-2-one
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Antineoplastic Agents
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Naphthalenes
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Tubulin
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Tubulin Modulators