期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 15, 期 15, 页码 3551-3554出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2005.05.052
关键词
alkylating agents; antiproliferative activity; combretastatin A-4; chlorambucil; tubulin polymerization
A series of chimeric compounds bearing the combretastatin and the nitrogen mustard cores were synthesized. All the compounds were cytotoxic and inhibited tubulin polymerization. When combretastatin was joined to chlorambucil via an ester linkage, the resultant compound proved to be significantly more potent than the two compounds put together. When combretastatin was joined to nitrogen mustard via an ether linkage or when a true hybrid was synthesized, loss of potency was observed. Nonetheless, these latter compounds appeared to be more efficacious and surprisingly were able to inhibit tubulin depolymerization at high concentrations. (c) 2005 Elsevier Ltd. All rights reserved.
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