Facile synthesis and cytotoxicity of substituted uracil-1'(<i>N</i>)-acetic acid and 4-pyridone-1'(<i>N</i>)-acetic acid esters of 20(S)-camptothecins

A series of novel substituted uracil-1'(<i>N</i>)-acetic acid esters (<b>5</b>–<b>9</b>) and 4-pyridone-1'(<i>N</i>)-acetic acid esters (<b>10</b>–<b>11</b>) of 20(S)-camptothecins (CPTs) have been synthesized by the acylation method. All of these new esters were assayed for <i>in vitro</i> cytotoxicity against five human cancer cell lines A549, Bel7402, BGC-823, HCT-8 and A2780. The <i>in vitro</i> bioassay results showed that all the synthesized compounds <b>5</b>–<b>11</b> had cytotoxities that were higher than TPT and comparable to CPT on these five tumor cell lines, some of them even showed comparable or superior cytotoxic activity to CPT. The <i>in vitro</i> data exhibited the cytotoxicity of the ester depended on that of its parent compound. The ester <b>5</b>, <b>6</b>, <b>8</b>, <b>10</b>, <b>11</b> even possessed the cytotoxity activity comparable to or even a little better than CPT on A549, HCT-8 and A2780. The compound <b>11</b> had the same level of cytoxity on Bel7402 as that of CPT. Here the synthesis and the <i>in vitro</i> antitumor evaluation of a series of novel 20-<i>O</i>-linked substituted uracil-1'(<i>N</i>)-acetic acid and 4-pyridone-1'(<i>N</i>)-acetic acid esters derivatives of CPTs are reported.