The Tunable Functionality of alpha,beta-Unsaturated Carbonyl Compounds Enables Their Differential Application in Biological Systems

Abstract

alpha,beta-Unsaturated carbonyl compounds as potential drug candidates is a controversial topic since their potential Michael acceptor activity can lead to cell damage and cytotoxicity. Nevertheless, the alpha,beta-unsaturated carbonyl functionality can be employed as a tool to fine tune biological activity by directly manipulating this entity. Depending on their electronic properties, alpha,beta-unsaturated carbonyl functionalities display different reactivities, namely Michael addition, radical scavenging, oxidation or double bond isomerization. Modifying the alpha-position of the alpha,beta-unsaturated carbonyl system, a concept that has not been widely explored, could produce new, very interesting derivatives. Currently in drug development, irreversible binding in active sites has proven to be one answer to drug resistance in cancer treatment. Overall, natural products containing the alpha,beta-unsaturated carbonyl unit possess multiple biological activities that could be transferred into novel pharmaceutical agents.