B. Patro, M. Tyagi, Jayati Saha
Oct 1, 2010
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Influential Citations
29
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Quality indicators
Journal
Bioorganic & medicinal chemistry
Abstract
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 (IC(50)=5.26±1.20 μM) than curcumin (IC(50)=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.