Nuclear magnetic resonance based structure of the protoberberine alkaloid coralyne and its self-association by spectroscopy techniques

Coralyne is an important alkaloid due to its anti-cancer and other medicinal properties. It targets DNA in cells and acts as human topoisomerase-I poison, telomerase inhibitor and nucleic acid intercalator. It has high tendency to undergo self-association, which is a matter of concern for therapeutic applications. The understanding of its interaction with DNA requires precise knowledge of chemical shifts in Nuclear Magnetic Resonance (NMR) spectra besides self-association. The present study is the first report of a complete assignment of all (1)H/(13)C resonances in NMR spectra of coralyne in DMSO-d(6) using one dimensional (1)H/(13)C and two dimensional NMR experiments. The chemical shift of all proton and several (13)C resonances have also been obtained in D(2)O and ethanol-d(6). The same has been calculated using Density Functional Theory (DFT). NMR spectra of coralyne show upfield shift of 0.6–1.2 ppm in aromatic ring protons suggesting stacking interactions. Apart from 11 intra molecular NOE cross peaks in 2D (1)H–(1)H ROESY spectra, 3 short distance NOE correlations, H6–10OCH(3), H5–10OCH(3) and H12–16CH(3), give direct independent evidence of the formation of a stacked dimer. The absorbance, fluorescence, circular dichroism and fluorescence lifetime experiments conducted in the present investigations corroborate results obtained by NMR.