Abstract

Research in anticancer chemotherapy has produced outstanding results, and mean survival rates have significantly improved over the last ten years. Nevertheless, all approved drugs are still characterized by narrow therapeutic windows that result mainly from their high systemic toxicity combined with their marked lack of tumor selectivity. Medicinal chemistry responds to the resulting demands with new analogues of a lead drug, or by developing prodrugs. Prodrugs are inactive compounds, which are metabolized in the body, either chemically or enzymatically, in a controlled or predictable manner, to the active parent drug. This review describes the results of strategies in prodrug development, subdivided into the principal categories of anticancer agents. The chemical implementation of prodrug approaches is illustrated through selected drug candidates.

Keywords: Anticancer agents, bioactivation, chemotherapy, prodrugs, anticancer chemotherapy, prolonged treatment, liposomes, pharmacological effect, oxidatively transformed, intracellular hydrolysis, alkylating metabolite, isophosphoramide mustard, D-glucose molecule, aminopeptidase, hypoxic cells