Abstract
Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Colchicine / metabolism
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Colonic Neoplasms / drug therapy
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Drug Design
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Drug Screening Assays, Antitumor
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Female
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Humans
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Marine Toxins / chemistry*
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Marine Toxins / pharmacology*
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Mice
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Mice, Nude
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Models, Molecular
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Molecular Docking Simulation
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Structure-Activity Relationship
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Tubulin / drug effects
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Tubulin / metabolism
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Tubulin Modulators / pharmacology
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Xanthines / chemical synthesis*
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Xanthines / pharmacology*
Substances
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Antineoplastic Agents
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Marine Toxins
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Tubulin
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Tubulin Modulators
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Xanthines
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Colchicine