title: 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-1reveals 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 KSVand Kassshows 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 SC50value 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 IC50values 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.affiliation: Chemistry Research Centre, Mohamed Sathak Engineering College, Kilakarai 623 806, Tamilnadu, India; Department of Chemistry, Sethu Institute of Technology, Pulloor, Kariapatti 626 115, Tamilnadu, India.
authors.forename: M P
authors.initials: MP
authors.lastname: Kesavan
authors.affiliation: Chemistry Research Centre, Mohamed Sathak Engineering College, Kilakarai 623 806, Tamilnadu, India; Department of Chemistry, Sethu Institute of Technology, Pulloor, Kariapatti 626 115, Tamilnadu, India.
authors.forename: G G
authors.initials: GG
authors.lastname: Vinoth Kumar
authors.affiliation: Chemistry Research Centre, Mohamed Sathak Engineering College, Kilakarai 623 806, Tamilnadu, India.
authors.forename: J
authors.initials: J
authors.lastname: Dhaveethu Raja
authors.affiliation: School of Physics, Madurai Kamaraj University, Madurai 625 021, Tamilnadu, India.
authors.forename: K
authors.initials: K
authors.lastname: Anitha
authors.affiliation: Department of Microbiology, Sourashtra College, Madurai 625 004, Tamilnadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Karthikeyan
authors.affiliation: Chemistry Research Centre, Mohamed Sathak Engineering College, Kilakarai 623 806, Tamilnadu, India; Department of Chemistry, Sethu Institute of Technology, Pulloor, Kariapatti 626 115, Tamilnadu, India. Electronic address: mkuraji@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Rajesh
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D011758:Pyrroles / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D011758:Pyrroles; D011809:Quinones; C480761:luotonin A; D004247:DNA
keywords: Anticancer; Antimicrobial; Antioxidant; Cu(II) complexes; DNA binding; Luotonin A