Transferrin (Tf) can control the level of free iron as iron-binding blood plasma glycoprotein in biological fluids. Tf has been exploited in the recent years on account of the potential function as a drug carrier targeting to tumor cells. Cyanine dyes have been widely studied as photosensitizers. The binding mechanism of Tf with 3, 3′-di(3-sulfopropyl)-4, 5, 4′, 5′-dibenzo-9-ethyl-thiacarbocyanine triethylammonium salt (ETC) was characterized at varying pHs and temperatures by fluorescence, UV-Vis absorption, circular dichroism (CD), and molecular modeling methods. The results showed that the static fluorescence quenching occurred between Tf and ETC. It was found that ETC bound strongly with Tf with an intrinsic binding constant (K_a), in the order of 10⁷ m⁻¹. The thermodynamic parameters demonstrated that van der Waals force or hydrogen bonds were the major binding force. The binding of ETC-Tf caused the secondary conformational change of Tf with increasing the α-helix content in Tf, which was confirmed by the results of spectroscopic experiments. Molecular modeling revealed that ETC bound residues located in the N-lobe of Tf by van der Waals force and induced local structural changes of Tf. This study may provide the theoretical foundations for ETC as a probe to label Tf, which is further beneficial to the Tf-targeted drugs in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Carbazole and its derivatives have been widely utilized as a functional building block in the fabrication of the organic medicine, pesticides, materials, etc., because of their excellent solubility, stability and biological activity. In this paper, 1-(5-carboxypentyl)-4-(2-(N-ethyl-carbazole-3-yl) vinyl) pyridinium bromide with a large Stokes shift was synthesized and characterized by ¹H NMR and MS. The UV/vis absorption and fluorescence spectra in different solvents and at different pH values were investigated preliminarily. The photostability and thermostability were also studied and the results showed that the compound was stable. The compound was also used to label bovine serum albumin (BSA) and calf thymus (ct)DNA. The results showed that the fluorescence intensity is enhanced when labeling with BSA and the binding ability is stronger than ctDNA, making it may be used as a biological probe. Copyright © 2015 John Wiley & Sons, Ltd.

Compounds selectively binding and stabilizing G-quadruplex structures could inhibit the telomerase or down- regulate the oncogenes and may act as anti-cancer drugs. An alkaloid with non-flat structure, fangchinoline, showed to strongly stabilize the intermolecular and intramolecular parallel stranded G-quadruplex structure, increasing melting temperature by 20 and 23°C, respectively. The binding mode was investigated by using NMR and molecular modelling methods. Four human cell lines (HL-60, BGC-823, Bel-7402 and KB) were taken to test the anti-proliferation effects of fangchinoline and the IC₅₀ values were ranged from 16 to 32 µmol/L. These results showed that the fangchinoline or related moiety derivatives may represent a class of telomere-targeted agents as potential anti-cancer drugs.

Complexation between the primary carrier of ligands in blood plasma, human serum transferrin (Tf), and a cyanine dye, 3,3′-di(3-sulfopropyl)-4,5,4′,5′-dibenzo-9-phenyl-thiacarbocyanine-triethylam monium salt (PTC) was investigated using fluorescence spectra, UV/Vis absorption spectra, synchronous fluorescence spectra, circular dichroism (CD) and molecular dynamic docking. The experimental results demonstrate that the formation of PTC–Tf complex is stabilized by van der Waal's interactions and hydrogen bonds, and the binding constants were found to be 8.55 × 10⁶, 8.19 × 10⁶ and 1.75 × 10⁴ M⁻¹. Moreover, fluorescence experiments prove that the operational mechanism for the fluorescence quenching is static quenching and non-radiative energy transfer. Structural investigation of the PTC–Tf complexes via synchronous fluorescence spectra and CD showed that the structure of Tf became more stable with a major increase in the α-helix content and increased polarity around the tryptophan residues after PTC binding. In addition, molecular modeling highlights the residues located in the N-lobe, which retain high affinity for PTC. The mode of action of the PTC–Tf complex is illustrated by these results, and may provide an effective pathway for the transport and targeted delivery of antitumor agents. Copyright © 2015 John Wiley & Sons, Ltd.

A copper-catalyzed approach for the synthesis of 2-aryl-quinazolinones through a domino reaction involving C–C bond cleavage is described. This protocol involves intramolecular C–C bond cleavage to construct 2-aryl-quinazolinones, which may offer an alternative method to prepare medically important quinazolinone derivatives and a new strategy for C–C bond cleavage. Besides C–C bond cleavage, this domino reaction includes N-arylation and benzylic C–H amidation.

The ligands which can facilitate the formation and stabilize G-quadruplex structures have attracted enormous attention due to their potential ability of inhibiting the telomerase activity and halting tumor cell proliferation. It is noteworthy that the abilities of the quaternary benzophenanthridine alkaloids (QBAs), the very important G-quadruplex binders, in inducing the formation of human telomeric DNA G-quadruplex structures, have not been reported. Herein, the interaction between single-strand human telomeric DNA and three QBAs: Sanguinarine (San), Nitidine (Nit) and Chelerythrine (Che), has been investigated. Although these molecules are very similar in structure, they exhibit significantly different abilities in inducing oligonucleotide d(TTAGGG)₄ (HT4) to specific G-quadruplex structures. Our experimental results indicated that the best ligand San could convert HT4 into antiparallel G-quadruplex structure completely, followed by Nit, which could transform to mixed-type or hybrid G-quadruplex structure partially, whereas Che could only transform to antiparallel G-quadruplex structure in small quantities. The relative QBAs' inducing abilities as indicated by the CD data are in the order of San>Nit>Che. Further investigation revealed that the G-quadruplex structures from HT4 induced by QBAs are of intramolecular motif. And only sequences with certain length could be induced by QBAs because of their positive charges which could not attract short chain DNA molecules to close to each other and form intermolecular G-quadruplex. In addition, the factors that affect the interaction between HT4 and QBAs were discussed. It is proposed that the thickness of the molecular frame and the steric hindrance are the primary reasons why the subtle differences in QBAs' structure lead to their remarkable differences in inducing the formation of the G-quadruplex structures.

Single-stranded telomeric DNA tends to form a four-base-paired planar structure termed G-quadruplex. Although kinds of G-quadruplex structures in vitro have been documented in the presence of potassium or sodium, recognition of these DNA motifs (both in vitro and in vivo) is still an important issue in understanding the biological function of the G-quadruplex structures in telomeres as well as developing anticancer agents. Herein we address this important question through the distinctive properties of a supramolecular system of cyanine dye 3,3′-di(3-sulfopropyl)-4,5,4′,5′-dibenzo-9-methyl-thiacarbocyanine triethylammonium salt (MTC) upon binding to different DNA motifs. Interaction of MTC with hybrid/mixed G-quadruplex results in a set of unique spectrophotometric signatures which are completely different from those arising from binding to other DNA motifs. Furthermore, such feature could be extended to map the locations of DNAs on interface. Linear duplex and mixed G-quadruplex in human telomeres assembled on Au film and stained by MTC were directly recognized by confocal laser scanning microscopy (CLSM). All results suggested that MTC supramolecular system may be a good probe of specific G-quadruplex structure.

A potential targeting drug delivery system consisting of folate (FA), the targeting molecule, human serum albumin (HSA), the carrier, and mitoxantrone (MTO), the medicine, has been designed. Data obtained by UV absorption, fluorescence, and NMR techniques indicated the formation of ternary complexes and possible application to building a targeting drug delivery system by using FA, MTO and HSA. Furthermore, cytotoxicity assay indicated that the toxicity of the FA-HSA-MTO against PC-3 cell line was 79.95%, which was much higher than that of free MTO tested in totally the same conditions. About 30% increase of the toxicity should be owed to the targeting effect of FA. Thus, the feasibility and validity of a novel targeting drug delivery system, FA-HSA-MTO, was confirmed.