Synthesis and preliminary bioevaluation of novel E-ring modified acetal analog of camptothecin as cytotoxic agents

In an effort to improve the metabolic stability of the E-ring and decrease the toxicity of camptothecin (CPT), a novel cytotoxic acetal analog with 21-alkoxy groups was designed and synthesized. The preliminary results revealed that this class of compounds showed superior antiproliferative activity in vitro and moderate in vivo activity, while their topoisomerase I (Topo I) inhibitory activity was weakened significantly. The implications of these results within the current understanding of the structure–activity relationship of camptothecin are analyzed in detail. The obtained information provides insight into the role of the 21-carbonyl group in the binding of CPT to Topo I–DNA complex.

Novel E-ring acetal analogs of camptothecin as cytotoxic agents were designed and prepared. Most of these derivatives possessed superior in vitro antitumor activities and moderate in vivo inhibitory activity.Figure optionsDownload as PowerPoint slideHighlights
► E-ring modified acetal analogs of camptothecin were designed and synthesized.
► These compounds showed superior in vitro and moderate in vivo antitumor activity.
► The information provides insight into the role of the 21-carbonyl group of CPT.