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

Abstract

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