Luminescence and binding properties of two isoquinoline alkaloids chelerythrine and sanguinarine with ctDNA

The binding mode and mechanism of the interactions between two planar cationic alkaloids chelerythrine (Che) and sanguinarine (San) with calf thymus DNA (ctDNA) were systematically investigated at pH 5.40 using UV–vis absorption spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Che and San show strong fluorescence at 570 and 589 nm, respectively. Che displays fluorescence enhancement with ctDNA whereas the fluorescence of San is quenched on interaction with ctDNA. In addition, UV–vis spectra of both alkaloids show apparent hypochromicity and are bathochromic shifted, indicating that they could intercalate into ctDNA bases. The fluorescence polarization of Che and San increases in the presence of ctDNA, again implying the intercalation of two alkaloids with ctDNA. This conclusion was also supported by the results obtained from anion quenching and cyclic voltammetry. The binding constants of both alkaloids with ctDNA were calculated in the order of 105 L/mol. San binds with ctDNA 3-fold stronger than Che. The stoichiometric bindings are five nucleotides per Che or San. Electrostatic binding also exists between the alkaloids and DNA helix. Finally, theoretical calculations show that only certain parts of Che and San molecules intercalate into the DNA helix.

This paper attests that Che and San form stable complexes with ctDNA, and represents the first attempt to utilize CV and molecular calculation methods. UV, fluorescence titration, and CV measurements all show that Che and San interact with DNA mainly via intercalation. Electrostatic binding also exists. The affinity of Che for DNA is slightly weaker than that of San. The stiochiometry of the binding was determined to be five nucleotides per San and Che. Che and San intercalate to DNA with C, D ring and A, B ring part, respectively.Figure optionsDownload as PowerPoint slideHighlights
► This paper attests that Che and San exhibit significant bindings to calf thymus DNA.
► Experimental data show that Che and San interact with DNA mainly via intercalation.
► Electrostatic binding also exists.
► Studies support that San has higher binding affinity towards DNA as compared to Che.
► Molecular calculation shows that Che and San intercalate to DNA with different part.