| Abstract
| - A series of N-alkylamide analogues of the lavendustin A pharmacophore were synthesized andtested for inhibition of the epidermal growth factor receptor (EGFR) protein tyrosine kinaseand the nonreceptor protein tyrosine kinase Syk. Although several compounds in the serieswere effective inhibitors of both kinases, it seemed questionable whether their inhibitory effectson these kinases were responsible for the cytotoxic properties observed in a variety of humancancer cell cultures. Accordingly, a COMPARE analysis of the cytotoxicity profile of the mostcytotoxic member of the series was performed, and the results indicated that its cytotoxicityprofile was similar to that of antitubulin agents. This mechanism of action was supported bydemonstrating that most compounds in the series were moderately effective as inhibitors oftubulin polymerization. This suggests that the lavendustin A analogues reported here, as wellas some of the previously reported lavendustin A analogues, may be acting as cytotoxic agentsby a mechanism involving the inhibition of tubulin polymerization.
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