Background: The aminocoumarin antibiotic, novobiocin, is a natural product that inhibits
DNA gyrase, a bacterial enzyme involved in cell division.
Method: More recently, novobiocin was found to act also on eukaryotic cells by blocking the 90 kDa
heat shock protein (Hsp90). Hsp90 is a molecular chaperone, critical for folding, stabilization and activation
of many proteins, in particular oncoproteins responsible for cancer progression. As opposed to
the geldanamycin and radicicol, the known inhibitors of Hsp90 that bind to the N-terminal region, the
binding domain of novobiocin is localized in the C-terminal part of this protein. While the N-terminal
inhibition also leads to the induction of some pro-survival signals, C-terminal inhibitors in which prosurvival
responses are avoided and client degradation is maintained can be developed as a new class of
potential anticancer chemotherapeutics. Numerous novobiocin analogs have been designed in the
search for more potent compounds and some of them exhibit significantly enhanced anti-proliferative
activity versus the natural product, as evaluated by cellular efficacies against several cancer cell lines.
Conclusion: This review describes structure-activity-relationships of novobiocin analogs and some
biological data reported so far on the anticancer activity of these modified compounds.