Abstract
Chemotherapeutic agents generally suffer from off-target cytotoxicity in noncancerous cell types, leading to undesired side effects. As a result, significant effort has been put into identifying compounds that are selective for cancerous over noncancerous cell types. Our laboratory has recently developed a series of near-infrared (NIR) fluorophores containing a phosphinate functionality at the bridging position of a xanthene scaffold, termed Nebraska Red (NR) fluorophores. Herein, we report the selective cytotoxicity of one NR derivative, NR744, against HeLa (cervical cancer) cells versus NIH-3T3 (noncancerous fibroblast) cells. Mechanistic studies based on the NIR fluorescence signal of NR744 showed distinct subcellular localization in HeLa (mitochondrial) versus NIH-3T3 (lysosomal) that resulted from the elevated mitochondrial potential in HeLa cells. This study provides a new, NIR scaffold for the further development of reagents for targeted cancer therapy.
Original language | English (US) |
---|---|
Pages (from-to) | 1712-1716 |
Number of pages | 5 |
Journal | ChemBioChem |
Volume | 20 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 2019 |
Keywords
- apoptosis
- cancer
- cytotoxicity
- fluorescence probes
- phosphinate
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Organic Chemistry