Carboranyl Analogues of Ketoprofen with Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines

Ketoprofen is a widely used nonsteroidal
anti-inflammatory drug
(NSAID) that also exhibits cytotoxic activity against various cancers.
This makes ketoprofen an attractive structural lead for the development
of new NSAIDs and cytotoxic agents. Recently, the incorporation of
carboranes as phenyl mimetics in structures of established drugs has
emerged as an attractive strategy in drug design. Herein, we report
the synthesis and evaluation of four novel carborane-containing derivatives
of ketoprofen, two of which are prodrug esters with an nitric oxide-releasing
moiety. One of these prodrug esters exhibited high cytostatic activity
against melanoma and colon cancer cell lines. The most pronounced
activity was found in cell lines that are sensitive to oxidative stress,
which was apparently induced by the ketoprofen analogue.