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 H/C resonances in NMR spectra of coralyne in DMSO-d using one dimensional H/C and two dimensional NMR experiments. The chemical shift of all proton and several C resonances have also been obtained in DO and ethanol-d. 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 H-H ROESY spectra, 3 short distance NOE correlations, H6-10OCH, H5-10OCH and H12-16CH, 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.