Binding Of 3a Research Articles

Nitroquinolone Fused Salicyl and Naphthyl Hydrazone Fluorescent Probes for the Detection of Fe3+and Pb2+ Ions.

The application of quinolones stretches over a large umbrella of medicinal field as well as chemosensor due to the presence of privileged heterocyclic aromatic rig system. Salicyl and Naphthyl Hydrazide motifs are also established fluorophore groups. Therefore in this work, we have designed and synthesized Salicyl hydrazide (3a-c) and naphthyl hydrazide fused nitroquinolones (5a-c) investigated for their fluorescent behaviour. Preliminary UV- absorption studies were carried out and the metal selectivity were examined with various metal ion. Among them, it was found that compound 3a was selective towards Fe3+ ions (λex = 330nm, 1:1 DMF:H2O at pH = 7.4 in HEPES Buffer medium). 3a shows decrease emission intensity in presence of Fe3+ ions. Compound 5a shows enhancement in fluorescence intensity upon addition of Pb2+ ion (λex = 280nm, 1:1 DMF:H2O at pH = 7.4 in HEPES Buffer medium). Further, the concentration dependence, competitive binding and EDTA reversibility were studied for selected compounds towards the respective cations selectivity. Jobs plot analysis indicate that 1:1 binding of 3a with Fe3+ ion (Ka = 3.17 x104M-1 and Limit Of Detection (LOD) = 5.1 × 10-7 M) whereas 5a showed 1:2 binding mode with Pb2+ ions (Ka = 2.14 × 106M-1 and Limit Of Detection (LOD) = 2.613 × 10-9M). Density Function Theoretical studies were performed as support for the experimental results.

Novel triazole and morpholine substituted bisnaphthalimide: Synthesis, photophysical and G-quadruplex binding properties

Four bisnaphthalimides derivatives 3a, 3b, 5a and 5b with polyamine linkage have been synthesized and characterized. Different spectroscopic techniques, including UV–Vis spectroscopy, fluorescence spectroscopy, circular dichroism and fluorescence resonance energy transfer (FRET), have been used to explore the interaction of these compounds with G-quadruplex structures (Htelo, c-myc, c-kit). The compounds 3a, 3b and 5b show high affinity toward Htelo, c-myc and c-kit G-quadruplexes (Ka > 4.42 × 106 M−1), and exhibit more than 40-fold selectivity for the quadruplex versus CT DNA. Binding of 3a, 3b to telomeric and oncogenic G-quadruplexes induce strong enhancement of the fluorescence intensity (18–27-fold), whereas the duplex CT DNA induces much weaker fluorescence enhancement (around 2-fold). Being fluorescent, the cellular localization of 3a, 3b can be conveniently tracked by fluorescence imaging. The results indicate that 3a, 3b can readily be taken up by A549 lung cancer cells. Molecular docking studies indicate that 3a, 3b, 5a and 5b mainly bind in the groove and/or loop region of the G-quadruplexes, and hydrogen bonding plays an important role in the interaction of bisnaphthalimide derivatives with G-quadruplexes. CD spectroscopy and FRET melting assay indicate that 3a, 3b and 5b can promote the formation and the stabilization of human telomeric and c-myc G-quadruplex DNA. The compound 3b can inhibit the growth of A549 cells (IC50 = 0.15 μM), with a much higher antitumor activity than amonafide.

New (arene)ruthenium(II) complexes of 4‑aryl‑4H‑naphthopyrans with anticancer and anti-vascular activities

A series of four 2‑amino‑3‑cyano‑4‑(3/4‑pyridyl)‑4H‑benzo[h]chromenes 2a–d and their dichlorido(p‑cymene)ruthenium(II) complexes 3a–d were tested for antiproliferative, vascular-disruptive, anti-angiogenic and DNA-binding activity. The coordination of the 4‑pyridyl‑4H‑naphthopyrans 2 to ruthenium led to complexes with pleiotropic effects. Unlike the free ligands 2a–d, their ruthenium complexes 3a–d showed a significant affinity for DNA as demonstrated by electrophoretic mobility shift assays (EMSA) and ethidium bromide assays. Binding of 3a–d to calf thymus DNA proceeded about 10-times faster compared with cisplatin. Treatment of HT-29 colon carcinoma, 518A2 melanoma and MCF-7Topo breast cancer cells with 3a and 3b caused an accumulation of cells in the G2/M phase and an increase of the fraction of mitotic cells in the case of HT-29, due to alterations of the microtubule cytoskeleton as shown by immunofluorescence staining. Complexes 3b–c showed a dual effect on the vascular system. They suppressed angiogenesis in zebrafish embryos and they destroyed the vasculature of the chorioallantoic membrane (CAM) in fertilized chicken eggs. They also inhibited the vasculogenic mimicry, typical of U-87 glioblastoma cells in tube formation assays.

Oxacalix[2]arene[2]triazine Derivatives with Halogen Bond Donors: Synthesis, Structure, and Halide Binding in the Solid State

By means of post-macrocyclization functionalization, a series of oxacalix[2]arene[2]triazine derivatives 3a–d, bearing mono- and dihalogen (Br, I) substituted phenyl moieties on the larger rim of the triazine rings were very efficiently synthesized with yields of 85–89%. The binding of 3a–d toward halide anions in the solid state was investigated by X-ray crystallography. For complexation of 3c (X = H, X′ = I) with chloride, a Cl–···H2O···Cl–···H2O···H2O pentagonal hydrogen bond network was found included in the cavity of the host molecule, as stabilized by cooperative anion-π interaction and halogen and hydrogen bonding. In contrast, with iodide only intermolecular halogen bonding between 3c and iodide was observed. On the other hand, 3d (X = X′ = I) forms a series of very similar chelating halogen bonding motifs with chloride, bromide, and iodide, respectively.

Rational design of substituted tripyrrole peptides that complex with DNA by both selective minor-groove binding and electrostatic interaction with the phosphate backbone.

The structures of the compounds we call 3a, 3b, and 3c-compounds that incorporate (i) the tripyrrole peptide of the minor-groove-binding distamycin class of compounds and (ii) polyamine ligands that extend from the minor groove and can interact with phosphodiester bonds--were arrived at by computer-graphics designing by using the x-ray structure of distamycin A complexed in the minor groove of d(CGCAAATTTGCG)2. Compounds 3a, 3b, and 3c are elaborations of distamycin analog 2, designed for improved stability in solution and easier synthesis and purification, which itself binds weakly to DNA. Compounds 3a, 3b, and 3c have been synthesized, and the interaction of distamycin A, 2, 3a, 3b, and 3c with calf thymus DNA, poly(dA-dT), poly(dG-dC), poly(dI-dC), pBR322 superhelical plasmid DNA, and, in the case of 3b, T4 coliphage DNA have been studied. The following pertinent conclusions can be drawn. Binding of 3a, 3b, and 3c occurs in the minor groove of DNA and, because of favorable electrostatic interaction of diprotonated polyamine side chains and DNA phosphodiester linkages, the tenacity of DNA binding and site specificity of 3a, 3b, and 3c are comparable to that of native distamycin A. 3b has been found to induce changes in the superhelical density of pBR322 plasmid DNA. The study establishes that the central pyrrole N-CH3 substituent of 2 can be replaced by bulky polyamine metal ligands to create any number of compounds that bind into the minor groove at A + T-rich sites and are putative catalysts for the hydrolysis of DNA.