Anticancer activities, structure-activity relationship, and mechanism of action of 12-, 14-, and 16-membered macrolactones.

Cancer remains one of the major causes of death worldwide despite the encouraging breakthroughs in the discovery of novel chemotherapeutic agents in recent years. The development of new effective anticancer candidates still represents a challenging endeavor due to the severe anticancer demands and the emergence of drug-resistant, especially multidrug-resistant, cancers. Macrolactones could regulate multiple signaling pathways in cancer cells and demonstrated potential anticancer effects, including inhibition of proliferation, metastasis, and angiogenic activity. Accordingly, macrolactones possess excellent efficacy against both drug-sensitive and drug-resistant cancer cells, and the rational design of macrolactones may provide valuable therapeutic interventions for cancers. The purpose of this review is as follows: (1) outline the recent advances made in the development of 12-, 14-, and 16-membered macrolactones with anticancer potential; (2) summarize the structure-activity relationship; and (3) discuss their anticancer mechanisms.