Conformationally based design of macrocycles as antitumor agents.

A key feature for any chemotherapeutic agent is a favorable conformation when it is presenting itself to its intended target. Numerous macrocycles have been identified as having antitumor activity and have been a source of lead compounds in anticancer research. The macrocyclic scaffold restricts bond rotation, therefore macrocycles maintain a relatively rigid conformation compared to their linear counterparts. This review discusses recent progress in the development of macrocyclic versions of linear compounds with known antitumor activity, and describes how restrictions in molecular conformation affect tumor inhibition.