Increasing recognition of the importance of aldehyde oxidase in drug development and discovery

Abstract

Aldehyde oxidases are molybdoflavoenzymes with broad substrate specificity, oxidizing different types of aldehydes, and heterocyclic rings. The physiological function of aldehyde oxidases is largely unknown, although the enzymes play an important role in the metabolism of numerous compounds of medicinal and toxicological interest, as they oxidize a wide range of aldehydes and heterocyclic compounds. In this article, we review the significance of aldehyde oxidases for the design and development of new drugs and discuss associated problems. These include species-specific differences in the complement of isoenzymes synthesized and general difficulties in studying the enzymatic characteristics of purified or recombinant aldehyde oxidases. We highlight the potential offered by human aldehyde oxidase targeting for the development of new pharmacological agents, limiting our attention to the realms of antiobesity and anti-cancer drugs. The last point is discussed in the context of the design of novel anticancer drugs, selectively activated or inactivated by this enzyme, with the final aim of achieving organ and/or tumor selectivity.

Keywords::

• AOX1
• molybdenum
• drug metabolism
• obesity
• cancer
• prodrugs
• xanthine oxidase

Acknowledgments

The authors would like to thank Felice Deceglie and Alessandro Soave for the artwork.

Declaration of interest

The Financial support of the Associazione Italiana Ricerca contro il Cancro (AIRC), Ministero della Università e della Ricerca, Fondazione “Italo Monzino,” and Fondazione “Negri-Weizmann” made this work possible.