Interactions of newly designed dicationic carbazole derivatives with double-stranded DNA: syntheses, binding studies and AFM imaging.

The design of small molecular ligands able to bind with DNA is pivotal for the development of diagnostic agents and therapeutic drugs targeting DNA. Carbazole-derivatives are potential agents against tumors and opportunistic infections of AIDS. Here, two carbazole-derived dicationic compounds, DPDI and DPPDI, were designed, synthesized and characterized using NMR, IR and MS. The DNA binding properties of DPDI and DPPDI were sensitive to ionic strength. At low ionic strength, planar and aromatic DPDI had a strongly intercalative interaction with DNA, which was confirmed by circular dichroism (CD) and gel electrophoresis. In DPPDI, a phenyl group substituting H atom at the –NH group of DPDI destroyed molecular planarity, which resulted in no intercalative interactions between DPPDI and DNA, proved by CD. The positive enhancement of CD at 260–270 nm and Hoechst 33258 competitive binding tests indicated the strong groove interactions of both DPPDI and DPDI to DNA. The similarity and difference in the structures between DPDI and DPPDI explained different interaction preferences with DNA. In groove interactions, dications of pyridinium on either DPDI or DPPDI could interact with DNA base pairs, and –NH on DPDI or –N–Ph on DPPDI pointed out of the groove, as the classical model of DNA groove binding agents. Furthermore, AFM imaging revealed that both carbazole-derivatives drove the DNA conformation more compact. All the experimental data proved that the two dicationic carbazole-derivatives interacted with DNA strongly and might act as a novel type of DNA-binding candidate.

[1]  S. Chakravorti,et al.  Modification of a styryl dye binding mode with calf thymus DNA in vesicular medium: from minor groove to intercalative. , 2012, The journal of physical chemistry. B.

[2]  Jongjin Park,et al.  Systematic investigation on the central metal ion dependent binding geometry of M-meso-tetrakis(N-methylpyridinium-4-yl)porphyrin to DNA and their efficiency as an acceptor in DNA-mediated energy transfer. , 2012, The journal of physical chemistry. B.

[3]  I. Piantanida,et al.  Interactions of multicationic bis(guanidiniocarbonylpyrrole) receptors with double-stranded nucleic acids: syntheses, binding studies, and atomic force microscopy imaging. , 2012, Chemistry.

[4]  Hong Liu,et al.  A 2,7-carbazole-based dicationic salt for fluorescence detection of nucleic acids and two-photon fluorescence imaging of RNA in nucleoli and cytoplasm. , 2011, Organic & biomolecular chemistry.

[5]  B. Juskowiak,et al.  The synthesis and spectral properties of new DNA binding ligands , 2010 .

[6]  Yalin Tang,et al.  The binding modes of carbazole derivatives with telomere G-quadruplex , 2010 .

[7]  Baibiao Huang,et al.  Two-photon fluorescence imaging of DNA in living plant turbid tissue with carbazole dicationic salt. , 2010, Organic & biomolecular chemistry.

[8]  K. Cheah,et al.  Cyanines as new fluorescent probes for DNA detection and two-photon excited bioimaging. , 2010, Organic letters.

[9]  P. Lou,et al.  G-Quadruplex Stabilizer 3,6-Bis(1-Methyl-4-Vinylpyridinium)Carbazole Diiodide Induces Accelerated Senescence and Inhibits Tumorigenic Properties in Cancer Cells , 2008, Molecular Cancer Research.

[10]  L. Ji,et al.  Synthesis, characterization, DNA-binding and spectral properties of complexes [Ru(L)4(dppz)]2+ (L=Im and MeIm). , 2008, Journal of inorganic biochemistry.

[11]  S. Pal,et al.  Dynamics in the DNA recognition by DAPI: exploration of the various binding modes. , 2008, The journal of physical chemistry. B.

[12]  N. Degtyareva,et al.  DNA conformational effects on the interaction of netropsin with A-tract sequences. , 2007, Biochemistry.

[13]  P. Peixoto,et al.  Design of DNA minor groove binding diamidines that recognize GC base pair sequences: a dimeric-hinge interaction motif. , 2007, Journal of the American Chemical Society.

[14]  Zhishu Huang,et al.  Spectroscopic studies of DNA binding modes of cation-substituted anthrapyrazoles derived from emodin. , 2007, European journal of medicinal chemistry.

[15]  Ruina Shi,et al.  Multiple binding modes for dicationic Hoechst 33258 to DNA. , 2007, The journal of physical chemistry. B.

[16]  Ali Akbar Saboury,et al.  Stability and structural features of DNA intercalation with ethidium bromide, acridine orange and methylene blue , 2007 .

[17]  Jian-Dong Jiang,et al.  Synthesis and structure-activity relationships of carbazole sulfonamides as a novel class of antimitotic agents against solid tumors. , 2006, Journal of medicinal chemistry.

[18]  Zao-ying Li,et al.  Binding and photocleavage of cationic porphyrin-phenylpiperazine hybrids to DNA. , 2006, Biophysical chemistry.

[19]  M. Saito,et al.  DNA condensation monitoring after interaction with hoechst 33258 by atomic force microscopy and fluorescence spectroscopy. , 2004, Journal of biochemistry.

[20]  Christian Bailly,et al.  Targeting DNA with novel diphenylcarbazoles. , 2004, Biochemistry.

[21]  P. Lou,et al.  A Novel Carbazole Derivative, BMVC: a Potential Antitumor Agent and Fluorescence Marker of Cancer Cells , 2004, Chemistry & biodiversity.

[22]  C. Bailly,et al.  DNA binding to guide the development of tetrahydroindeno[1,2-b]pyrido[4,3,2-de]quinoline derivatives as cytotoxic agents. , 2004, Journal of medicinal chemistry.

[23]  Robert M Clegg,et al.  Base-sequence specificity of Hoechst 33258 and DAPI binding to five (A/T)4 DNA sites with kinetic evidence for more than one high-affinity Hoechst 33258-AATT complex. , 2002, Journal of molecular biology.

[24]  C. Bailly,et al.  Sequence-dependent binding of bis-amidine carbazole dications to DNA. , 2001, European journal of biochemistry.

[25]  W D Wilson,et al.  Effects of compound structure on carbazole dication-DNA complexes: tests of the minor-groove complex models. , 2000, Biochemistry.

[26]  Yang Zhao,et al.  Interaction of a novel red-region fluorescent probe, Nile blue, with DNA and its application to nucleic acids assay. , 1999, The Analyst.

[27]  W. Wilson,et al.  A new type of DNA minor-groove complex: carbazole dication-DNA interactions. , 1997, Biochemistry.

[28]  R. Fiel,et al.  Binding of meso-tetra (4-N-methylpyridyl) porphine to DNA. , 1980, Nucleic acids research.

[29]  L. Minchenkova,et al.  Different conformations of double‐stranded nucleic acid in solution as revealed by circular dichroism , 1973, Biopolymers.