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