Beyond the Antagonism: Self-Labeled Xanthone Inhibitors as Modeled “Two-in-One” Drugs in Cancer Therapy

Self-labeled inhibitors (SLIs) are
promising for creating links,
ranging from cancer therapy and metastatic pathways to mechanistic
elucidation. In this study, a new category of “two-in-one”
fluorescent xanthone inhibitors was developed for the systematic evaluation
of anticancer activity and the selective imaging of cytoplasm in vitro.
These xanthone inhibitors presented high fluorescent brightness, working
over a wide pH range enabled by a “switchable reaction”
of the heterocyclic backbone. The strength and nature of fluorescence
were probed via spectroscopic methods and density functional theory
calculations on the molecular level, respectively. Along with the
potent anticancer activity, which was demonstrated using MTT and clonogenic
assays with high fluorescent brightness in the cytoplasm, SLI 3fd could be established as a modeled self-monitoring drug
in cancer therapy.