Design, Synthesis, and Evaluation of Boron Dipyrromethene-Based Fluorescent Probes Targeting BRAF for Melanoma...

Fluorescent dyes are widely applied in clinical diagnosis, detection, and treatment of diseases. Several image probes such as ICG, MB, and 5-ALA have been approved by FDA. However, the limited tumor-targeting capability of these dyes hinders their effectiveness in oncological imaging. Currently, various ligand-based targeting probes have been developed to minimize nonspecific background emission. BRAF, especially BRAF V600E, is a common cancer gene and undergoes frequent mutation in melanoma. Small molecular BRAF kinase inhibitors have been approved for the treatment of melanoma patients carrying the BRAF V600E mutation, including Vemurafenib, Dabrafenib and so on. Boron dipyrromethene (BODIPY) as an important fluorescent class has been investigated extensively. Vemurafenib-BODIPY has been reported to visualize BRAF V600E mutated cancer cells. Herein, the designed BODIPY-based Vemurafenib derivatives targeting BRAF for cancer cell imaging are reported. The fluorescent probes are characterized and evaluated of photophysical properties, targeted binding and live cell imaging. Compound 1a exhibited promising fluorescence imaging ability. To improve fluorescence quantum yield, structural optimization is performed by incorporating meso N,N'-dialkyl-substituted amides to BODIPY core. Compound 1d shows excellent fluorescence properties and nice binding affinity. It allows visualization of BRAF V600E mutated cancer cells at low concentrations.