Novel Antimicrobial 8‑Hydroxyquinoline-Based Agents: Current Development, Structure–Activity Relationships, and Perspectives

The search for new antimicrobials
is imperative due to the emergent
resistance of new microorganism strains. In this context, revisiting
known classes like 8-hydroxyquinolines could be an interesting strategy
to discover new agents. The 8-hydroxyquinoline derivatives nitroxoline
and clioquinol are used to treat microbial infections; however, these
drugs are underused, being available in few countries or limited to
topical use. After years of few advances, in the last two decades,
the potent activity of clioquinol and nitroxoline against several
targets and the privileged structure of 8-hydroxyquinoline nucleus
have prompted an increased interest in the design of novel antimicrobial,
anticancer, and anti-Alzheimer agents based on this class. Herein,
we discuss the current development and antimicrobial structure–activity
relationships of this class in the perspective of using the 8-hydroxyquinoline
nucleus for the search for novel antimicrobial agents. Furthermore,
the most investigated molecular targets concerning 8-hydroxyquinoline
derivatives are explored in the final section.