High-Throughput Screening for the Discovery of Iron Homeostasis Modulators Using an Extremely Sensitive Fluorescent Probe.

High-throughput methods for monitoring subcellular labile Fe(II) are important for conducting studies on iron homeostasis and for the discovery of potential drug candidates for the treatment of iron deficiency or overload. Herein, a highly sensitive and robust fluorescent probe for the detection of intracellular labile Fe(II) is described. The probe was designed through the rational optimization of the reactivity and responsiveness for an Fe(II)-induced fluorogenic reaction based on deoxygenation of an N-oxide, which was developed in-house. The probe is ready to use for a 96-well-plate-based high-content imaging of labile Fe(II) in living cells. Using this simple method, we were able to conduct high-throughput screening of a chemical library containing 3399 compounds. The compound lomofungin was identified as a potential drug candidate for the intracellular enhancement of labile Fe(II) via a novel mechanism in which the ferritin protein was downregulated.

Bismuth-rhodamine: a new red light-excitable photosensitizer.

Bismuth-rhodamine (BiR) was developed as a new photosensitizer scaffold, and its photophysical properties were evaluated. BiR showed significant red-shifted absorption and emission compared with other xanthene-based photosensitizers, together with an efficient quantum yield for the generation of 1O2. BiR showed efficient cell-permeability as well as photo-triggered generation of 1O2 in cells.