Synthesis, cytotoxicity study of novel bisacridine derivatives and their interaction with c-myc promoter G-quadruplex/i-motif

Abstract

Objective

To synthesize novel bisacridine derivatives A1-A4 and study cytotoxicity and their interaction with c-myc G-quadruplex/i-motif DNA.

Method

Bisacridines A1-A4 were synthesized according to the conventional reaction method. Fluorescence resonance energy transfer (FRET) melting assay, Surface Plasmon Resonance (SPR) measurement, CD experiments, and molecular docking were used to study the interactions between A1-A4 and c-myc promoter G-quadruplex/i-motif. MTT cytotoxicity assay was used to evaluate the cytotoxicity of the bisacridine derivatives A1-A4 against A375, Hela, A549, U2OS, HCT116, Siha, HuH7 cell lines.

Result

The results of FRET melting assay and SPR measurement indicated that bisacridine derivatives A1-A4 could bind to and stabilize the c-myc G-quadruplex/i-motif structure. CD experiments and molecular docking results demonstrated the interaction between A1-A4 and c-myc G-quadruplex/i-motif. MTT experiments showed that A1-A4 exhibited strong inhibitory effects on the proliferation of human A375, Hela, A549, U2OS, HCT116, Siha, HuH7 cell lines.

Conclusion

Bisacridine derivatives A1-A4 could bind to and stabilize the c-myc G-quadruplex/i-motif to inhibit the proliferation of human cancer cells and will potentially be developed into a class of small molecule ligands targeting c-myc G-quadruplex/i-motif.