How do quinolones/ floroquinolones work?

I know they inhibit nucleic acid replication and transcription, but how? Do they interfere with a specific enzyme (helicase, polymerase, ligase etc)?

1 Answer
Mar 19, 2017

Quinolones are a family of synthetic broad spectrum antibiotic drugs.


Flouro quinolones have a fluorine atom attached to the central quinolone ring, and play an important role in the treatment of serious bacterial infection.

Quinolones and fluoroquinolones inhibit bacterial replication by blocking their DNA replication pathway.

Unwinding of DNA is important for the synthesis of proteins aswell as DNA replication. This is brought about by enzymes of the topoisomerase II type. Quinolones and fluoroquinolones inhibit this enzyme. They alter the activate site of the enzyme and prevent them from reacting with its substrate. Due to this the bacteria is unable to replicate or synthesise proteins.

Fluoroquinolones enter the cells through porins and can target intracellular pathogens. These usually selectively inhibit the topoisomerase II ligase domain, leaving the two nuclease domains intact. Along with the constant action of the topoisomerase II in the bacterial cell, this modification leads to DNA fragmentation via the nucleasic activity of the intact enzyme domain.