Benzothiazole Derivatives Targeting G-Quadruplex DNA: Synthesis, DNA Interaction and Living Cell Imaging

The small molecule fluorescence probes for G-quadruplexes (G4) play a vital role in the detection of G4. In this work, two novel D-pi-A benzothiazole derivatives were synthesized, and their interactions with different secondary structure DNA, cytotoxicity, and intracellular distribution were investigated in detail. Both compounds have a high affinity and about 100-fold turn-on fluorescence response to the promoter G4 in buffer solution, moreover, the compound also stabilizes effectively the promoter G4 structure. Besides, both compounds have no influence on the conformation of the promoter G4, but they induce the folding of bcl-2 from the coiled chain into the mixed-type G4 in salt-free buffer solution. The binding stoichiometries of the compound to bcl-2, c-kit2, and c-myc G4 are near 2 : 1, 1 : 1, and 3 : 1, respectively, and the interactions are an enthalpy-driven process. Furthermore, both compounds inhibit the proliferation of HepG2 cells, with IC50 values of 3.23 and 38.9 mu M. The compound mainly distributes in the cytoplasm of living cells and might interact with DNA. The current results provide the valuable information for design of fluorescence probes targeting G4 in the living cell.

Automated summary

In this study, two novel D-pi-A benzothiazole derivatives were synthesized and their interactions with different DNA structures, cytotoxicity, and intracellular distribution were investigated. These compounds showed high affinity for the promoter G4 and exhibited strong fluorescence response in buffer solution.