Abstract
A series of novel hybrid compounds obtained by the attachment of anhydrovinblastine, vinorelbine, and vindoline to thiocolchicine, podophyllotoxin, and baccatin III are described. Two types of diacyl spacers are introduced. The influence of the hybrid compounds on tubulin polymerization is reported. The results highlight the importance of the length of the spacer. Immunofluorescence microscopy and flow cytometry measurements that compound with the best in vitro activity could disrupt microtubule networks in cell and prevent the formation of the proper spindle apparatus, thereby causing cell cycle arrest in the G2/M phase. The newly synthesized compounds were tested in the human lung cancer cell line A549.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / chemical synthesis*
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Alkaloids / toxicity
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / toxicity
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Antineoplastic Agents, Phytogenic / chemical synthesis
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Antineoplastic Agents, Phytogenic / toxicity
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Cell Line, Tumor
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Colchicine / analogs & derivatives*
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Colchicine / chemical synthesis
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Colchicine / toxicity
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Combinatorial Chemistry Techniques
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Dimerization
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Drug Design
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Humans
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Podophyllotoxin / chemical synthesis*
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Podophyllotoxin / toxicity
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Radiation-Sensitizing Agents / chemical synthesis
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Radiation-Sensitizing Agents / toxicity
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Swine
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Taxoids / chemical synthesis*
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Taxoids / toxicity
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Tubulin / metabolism*
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Tubulin Modulators / chemical synthesis*
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Tubulin Modulators / toxicity
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Vinblastine / analogs & derivatives*
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Vinblastine / chemical synthesis*
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Vinblastine / toxicity
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Vinorelbine
Substances
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Alkaloids
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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Radiation-Sensitizing Agents
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Taxoids
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Tubulin
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Tubulin Modulators
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baccatin III
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thiocholchicine
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vindoline
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Vinblastine
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Podophyllotoxin
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Vinorelbine
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Colchicine