Comparative nuclease and anti-cancer properties of the naturally occurring malabaricones

The nuclease activities of the malabaricones have been studied so as to establish a structure–activity correlation and deduce the mechanistic pathway of the process. The inactivity of malabaricone A and malabaricone D revealed that the resorcinol moiety, present in the malabaricones did not contribute to the nuclease activity. Amongst the test compounds, malabaricone C (mal C) containing a B-ring catechol moiety showed significantly better Cu(II)-dependent nuclease activity than the partially methylated catechol derivative, mal B and curcumin. Mal C was found to bind efficiently with Cu(II) and DNA to facilitate the DNA nicking via a site-specifically generated Cu(I)-peroxo complex. Consistent with its Cu(II)-dependent nuclease property, mal C showed better cytotoxicity (IC50 = 5.26 ± 1.20 μM) than curcumin (IC50 = 24.46 ± 3.32 μM) against the MCF-7 human breast cancer cell line. The mal C-induced killing of the MCF-7 cells followed an apoptotic pathway involving oxidative damage to the cellular DNA.

Consistent with its Cu(II)-mediated nuclease property, mal C could efficiently (IC50 ∼5 μM) induce killing of the MCF-7 human breast cancer cell line via oxidative damage to cellular DNA.Figure optionsDownload as PowerPoint slide