NQO1-responsive Prodrug for in Cellulo Release of Cytochalasin B as Cancer Cell-targeted Migrastatic

Migrastatic drugs targeting cell motility and thereby suppress invasiveness of solid cancer cells, including their ability to metastasize and establish secondary tumors, are of high interest and have the potential to bring about a paradigm shift in the treatment of solid cancer. Cytochalasans, such as cytochalasin B, are known to disrupt cytoskeletal dynamics by inhibiting actin polymerization and have attracted considerable attention as potential migrastatics over the last decades, but are limited by selectivity issues so far. We herein report on the design, synthesis and evaluation of a bioresponsive prodrug BQTML-CB cleavable by the quinone-oxidoreductase NQO1, discussed as therapeutic target for the treatment of cancer.