Clofazimine is not a fluoroquinolone #120
Description
Hello,
Thanks for all the work you do keeping CARD up and up-to-date! I just wanted to bring to your attention a small issue I noted with the clofazimine entry in CARD
The current definition states "Clofazimine is a fluoroquinolone-class phenazine dye used for the treatment of leprosy. Clofazimine binds to DNA and disrupts bacterial DNA gyrase, thereby causing double-stranded DNA breaks, and subsequent cell death." The wikipedia page on clofazimine also cites the same 1995 article as used in CARD arguing for a DNA intercalation mechanism, so I imagine that whatever is in that paper started the confusion. Unfortunately, I can't access the full text of the 1995 paper.
However, regardless of mechanism, clofazimine is not a fluoroquinolone; the fluoroquinolones are derivatives of 4-quinolone, whereas clofazimine does not contain any 4-quinolone substructure. I suspect the confusion came from two things: (1) fluoroquinolones act by intercalating into the DNA as it is being coiled or uncoiled by DNA gyrase/topoisomerase and (2) this 1995 paper postulates a similar mechanism of action for clofazimine.
More recent papers such as this 2023 review or this 2012 review reflect the current understanding of the mechanism of action as more likely involving the bacterial outer membrane. I would propose an updated definition that is something like:
"Clofazimine is a lipophilic riminophenazine dye used for the treatment of leprosy as well as drug-resistant tuberculosis. The exact mechanism of clofazimine is unknown, although it is believed to involve disruption of the bacterial outer membrane."