Evolution in medicinal chemistry of E-ring-modified Camptothecin analogs as anticancer agents

•CPT is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme Topo I.•CPT analogs with modification of the E-ring lactone are reviewed.•This review provides insight into the structural characteristics of ring E.•HCPTs and non-lactone, five-membered ketones are becoming more attractive agents.

Camptothecin (CPT), a natural topoisomerase (Topo) I inhibitor, exhibits powerful antineoplastic activity against colorectal, breast, lung and ovarian cancers. However, the poor solubility and the inherent instability of the lactone E-ring in physiological pH resulted in low therapeutic efficacy and severe toxicity. In the past several decades' substantial progress toward understanding its pharmacology, lots of analogs have been prepared to overcome its drawbacks. The review provides a detailed discussion of the evolution in medicinal chemistry of CPT analogs with modification of the E-ring lactone.

Graphical abstractThe evolution in medicinal chemistry of E-ring-modified CPT analogs is clustered into four classes, providing insight into the structural characteristics of ring E that are responsible for antitumor activity.Figure optionsDownload full-size imageDownload as PowerPoint slide