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

Abstract

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)H2OCl]Cl (1) and [Cu(L)2]Cl2 (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 5nm with the DNA binding affinity of Kb, 8.65×103M-1, but complex 2does not show any red-shift with binding constant Kb, 7.32×103M-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 KSV and Kass 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±0.69μM 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 24hrs are 1 (5.0±0.25, 12.0±0.30μM)<2 (6.5±0.27, 15.0±0.30μM)<L (7.0±0.15, 25.0±0.35μM) 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).

• Authors: M P Kesavan, G G Vinoth Kumar, J Dhaveethu Raja, K Anitha, S Karthikeyan, J Rajesh
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 167 Pg. 20-28 (Feb 2017) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 28039786 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Infective Agents
• Antineoplastic Agents
• Antioxidants
• Pyrroles
• Quinones
• luotonin A
• DNA

Topics

• Anti-Infective Agents (pharmacology)
• Antineoplastic Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Bacteria (drug effects)
• Cell Line, Tumor
• DNA (drug effects)
• Drug Screening Assays, Antitumor
• Fungi (drug effects)
• Humans
• Microbial Sensitivity Tests
• Pyrroles (pharmacology)
• Quinones (pharmacology)
• Spectrum Analysis (methods)