DNA interaction, antimicrobial, antioxidant and anticancer studies on Cu(II) complexes of Luotonin A

Luotonin A (L), a novel natural cytotoxic and anti-inflammatory alkaloid, chelated with copper(II) to improve its cytotoxic effect against the cancer cells. The complexes [Cu(L)H2OCI]CI (1) and [Cu(L)(2)]Cl-2 (2) are prepared by using copper(II) chloride and L with ligand/metal molar ratio of 1:1 and 2:1 respectively. A solution of complexes 1 & 2 are characterized by physical spectroscopic methods using Ultraviolet-visible (UV-Vis) spectrophotometer, Fourier Transform-Infra red (FT-IR) spectroscopy, Electron Para magnetic Resonance Spectroscopy (EPR) and by electrochemical methods. The interaction of these complexes 1 & 2 with calf thymus (CT-DNA) have been investigated by physical methods to propose the modes of DNA binding with the complexes 1 & 2. Absorption spectral titration studies of complex 1 with CT-DNA shows a red-shift of 5 nm with the DNA binding affinity of ICI 8.65 x 10(3) M-1, but complex 2does not show any red-shift with binding constant K-b, 7.32 x 10(3) M-1 reveals that the complex 1 binding with DNA strongly than complex 2 and the binding occurs in between the base pairs of DNA as intercalation. Strong interactions of the two complexes 1 & 2 with CT-DNA have also been confirmed by fluorescence spectral titration studies. The evaluated values of K-sv and K-ass shows that, the complexes 1 & 2 interact with DNA through the intercalation, coincide with other partial intercalators strongly than the free ligand L Complex 1 exhibits potent antioxidant activity with SC50 value of 23.9 +/- 0.69 mu M is evaluated by DPPH radical scavenging assay and which has potent antimicrobial activity against pathogens than 2 and L The anticancer activity of L, complexes 1 & 2 against human breast cancer cell line (MCF-7) and cervical cancer cell line (HeLa) has also been studied by using fluorescence staining method. The IC50 values of L, complexes 1& 2 against MCF-7 and HeLa cell lines with the incubation time intervals of 24 hrs are 1 (5.0 +/- 0.25, 12.0 +/- 0.30 mu M) < 2 (6.5 +/- 0.27,15.0 +/- 0.30 mu M) < L (7.0 +/- 0.15, 25.0 +/- 035 mu M) respectively. Interestingly, complex 1 exhibits anticancer activity more potent than L against both MCF-7 and HeLa cell lines. The result of anticancer activity studies show that the cytotoxic activity of L against MCF-7 and HeLa cells is increased, when chelated with Cu(II). (C) 2016 Elsevier B.V. All rights reserved.