Acidic Lysosome-Anchoring Croconium-Based Nanoplatform for Enhanced Triple-Mode Bioimaging and Fe-Triggered Tumor Synergistic Therapy.

Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe-modulated agent.

Water-solubility croconic acid-bisindole dye with morpholine ring for tumor NIRF/PA imaging and photothermal therapy activated by lysosome pH-response.

A novel croconic acid-bisindole dye CR-630 with a morpholine ring showed good water-solubility and obvious lysosome-targeting. The protonation of the nitrogen atom in the indole and lysosome-targeting of morpholine ring let it exhibit stronger pH-responsive NIR/PA imaging and photothermal effect in the lysosome acidic microenvironment (pH 4.0-5.

NIR C-Myc Pu22 G-quadruplex probe as a photosensitizer for bioimaging and antitumor study.

Despite the fact that C-Myc G-quadruplex in the oncogene promoter regions is one of the crucial targets of antitumor drugs, the selectivities and proliferation inhibitions of its probes towards tumor cells remain a big challenge. Until now, no effective C-Myc G-quadruplex probes have been reported as a photosensitizer to increase their antitumor activities. Here, the first NIR C-Myc G-quadruplex probe PDS-SQ has been designed, comprising a G-quadruplex binder PDS and a squaraine dye SQ as a photosensitizer.

G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor.

At present, there are still no anti-Zika virus (ZIKV) drugs or vaccines approved by FDA with accurate targets and antiviral mechanisms. Considering the RNA G-quadruplex sequences in ZIKV genome, it is very meaningful to develop G-quadruplex binders as potential anti-ZIKV drugs with novel and accurate targets. In this paper, five classical G-quadruplex binders including Ber, Braco 19, NiL, 360A and PDS have been chosen to discuss their interaction with ZIKV RNA G-quadruplexes.

Human telomere double G-quadruplex recognition by berberine-bisquinolinium imaging conjugates in vitro and cells.

Molecular tools of double or multimeric G-quadruplexes have been given higher requirements on detection sensitivity, thermal stabilization and cell imaging to establish functions of these G-quadruplex aggregates and biological mechanisms as anticancer reagents. Here, two smart berberine-bisquinolinium conjugates (Ber-360A and Ber-PDS) by linking the berberine fluorophore ligand and an established G-quadruplex binder (i.e.

Dimers formed with the mixed-type G-quadruplex binder pyridostatin specifically recognize human telomere G-quadruplex dimers.

By choosing pyridostatin (PDS) with high thermal stabilization towards mixed-type G-quadruplexes as the monomer in dimers, three novel polyether-tethered PDS dimers (1a-c) were first synthesized and their interaction with human telomere G-quadruplex dimers (G2T1) was studied. Through the regulation of the linker length in PDS dimers, the dimer with a medium-length polyether linker (1b) showed higher binding selectivity and thermal stabilization (ΔT = 29.5 °C) towards antiparallel G2T1 over G-quadruplex monomers (G1).

A Comparative Study on High Selectivities of Human Telomeric Dimeric G-Quadruplexes by Dimeric G-Quadruplex Binders.

Three new polyether-tethered bisquinolinium dimers (3 a-c) were synthesized, and their binding affinities, selectivities, and thermal stabilization towards dimeric G-quadruplex DNA (G2T1) in human telomeric regions were studied. The bisquinolinium dimer with a medium-length polyether linker (3 b) showed 30-425-fold higher binding affinity and selectivity towards antiparallel G2T1 than towards monomeric quadruplexes, which included human telomeric monomeric G-quadruplexes (G1), c-kit 1, c-kit 2, and c-myc. In addition, compound 3 b induced the formation of quadruplexes and displayed the highest level of thermal stabilization (ΔT >28.

A novel square-planar Pt(ii) complex as a monomeric and dimeric G-quadruplex DNA binder.

A novel phenanthroimidazole ethylenediamine Pt(ii) complex with coumarin derivative (1) was synthesized and showed higher affinity, selectivity and thermal stabilization for mixed-type dimeric G-quadruplexes (G2T1) over monomeric G-quadruplexes (G1) and duplex DNA. Complex 1 could bind to G-quadruplexes end-stacking and external-binding modes.

[ADS-J1 antagonizes semen-derived enhancer of virus infection-mediated enhancement of transmitted founder HIV-1 and its matched chronic control strain infection].

Objective: To investigate the effect of semen-derived enhancer of virus infection (SEVI) on the infection of transmitted/founder (TF) HIV-1 and its matched chronic control (CC) viruses and the antagonism of ADS-J1 on SEVI-mediated enhancement of TF and CC virus infection in vitro.

Methods: PAP self-assembling into SEVI amyloid fibrils was validated by ThT assay. We generated the virus stocks of TF and CC virus pair.

Specifically targeting mixed-type dimeric G-quadruplexes using berberine dimers.

Three polyether-tethered berberine dimers (1a-c) were studied for their binding affinity, selectivity and thermal stabilization towards human telomeric dimeric quadruplex DNA (G2T1). Compound 1a with the shortest polyether linker showed the highest affinity (K > 10 M) and 76-508-fold higher selectivity for mixed-type G2T1 over antiparallel G2T1 and three monomeric G-quadruplexes, which are human telomeric monomeric quadruplex G1, c-kit 1 and c-kit 2. Compound 1a induced the formation of quadruplex structures and showed higher thermal stabilization for mixed-type G2T1 than for anti-parallel G2T1, G1 and ds DNA.

Dinickel-Salphen Complexes as Binders of Human Telomeric Dimeric G-Quadruplexes.

Three new polyether-tethered dinickel-salphen complexes (2 a-c) have been synthesized and fully characterized by NMR spectroscopy, mass spectrometry, and elemental analyses. The binding affinity and selectivity of these complexes and of the parent mono-nickel complex (1) towards dimeric quadruplex DNA have been determined by UV/Vis titrations, fluorescence spectroscopy, CD spectroscopy, and electrophoresis. These studies have shown that the dinickel-salphen complex with the longest polyether linker (2 c) has higher binding affinity and selectivity towards dimeric quadruplexes (over monomeric quadruplexes) than the dinickel-salphen complexes with the shorter polyether linkers (2 a and 2 b).

Highly selective, sensitive and fluorescent sensing of dimeric G-quadruplexes by a dimeric berberine.

This paper describes the highly selective, sensitive and topology-specific fluorescent sensing of dimeric G-quadruplexes by a polyether-tethered dimeric berberine 1. Compound 1 displays high selectivity for dimeric G-quadruplexes over monomeric ones, and can be lit up by dimeric G-quadruplexes, in particular by the one linked with one TTA subunit. In addition, it shows no effect on the topology or thermal stability of the G-quadruplexes.

Does lipophilicity affect the effectiveness of a transmembrane anion transporter? Insight from squaramido-functionalized bis(choloyl) conjugates.

Six squaramido-functionalized bis(choloyl) conjugates were synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Their transmembrane anionophoric activity was investigated in detail by means of chloride ion selective electrode technique and pyranine assay. The data indicate that this set of compounds is capable of promoting the transmembrane transport of anions presumably via proton/anion symport and anion exchange processes, and that lipophilicity in terms of clog P from 3.

Synthesis and transmembrane anion/cation symport activity of a rigid bis(choloyl) conjugate functionalized with guanidino groups.

A rigid bis(choloyl) conjugate functionalized with guanidino groups was synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Its transmembrane ionophoric activity across egg-yolk l-α-phosphatidylcholine-based liposomal membranes was investigated by means of chloride ion selective electrode technique and pH discharge assay. The data indicate that under the assay conditions, this conjugate was capable of promoting the transport of anions, presumably via a cation/anion symport process.

Synthesis and anticancer activities of 3-arylflavone-8-acetic acid derivatives.

This paper describes the synthesis and the antiproliferative activities of compounds 9a-r, 3-aryl analogs of flavone-8-acetic acid that bear diverse substituents on the benzene rings at the 2- and 3-positions of the flavone nucleus. Their direct and indirect cytotoxicities were evaluated against HT-29 human colon adenocarcinoma cell lines, A549 lung adenocarcinoma cell lines and Human Peripheral Blood Mononuclear Cells (HPBMCs). The results indicate that most of the compounds bearing electron-withdrawing substituents (9b-m) exhibited moderate direct cytotoxicities.

Synthesis, hydrolytic DNA-cleaving activities and cytotoxicities of EDTA analogue-tethered pyrrole-polyamide dimer-based Ce(IV) complexes.

Two EDTA analogue-tethered C2-symmetrical dimeric monopyrrole-polyamide 5 and dipyrrole-polyamide 6, and their corresponding Ce(IV) complexes Ce-5 and Ce-6 were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicate that complexes Ce-5 and Ce-6 exhibited potent DNA-cleaving activities under physiological conditions. The maximal first-order rate constants (kmax's) were (0.

Synthesis and potent ionophoric activity of a squaramide-linked bis(choloyl) conjugate.

A squaramide-linked bis(choloyl) conjugate was synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Fluorescence and chloride ion selective electrode assays indicate that this compound exhibits potent ionophoric activity across egg-yolk L-α-phosphatidylcholine-based liposomal membranes, presumably via an anion-modulating anion-cation co-transport/symport process. A Hill analysis reveals that three molecules of this compound are assembled into the transport-active species.

Synthesis, DNA-cleaving activities and cytotoxicities of C₂-symmetrical dipyrrole-polyamide dimer-based Cu(II) complexes: a comparative study.

Two C₂-symmetrical dipyrrole-polyamide dimers 2 and 3 that were tethered with triethylenetetramine and spermine, respectively, and their corresponding Cu(II) complexes 2@Cu(2+) and 3@Cu(2+), were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicated that both Cu(II) complexes exhibited potent DNA-cleaving activities under physiological conditions, most probably via an oxidative mechanism. Kinetic assay indicate that 2@Cu(2+) and 3@Cu(2+) exhibited comparable catalytic efficiency with the Cu(II) complex of their 2,2'-(ethane-1,2-diylbis(oxy))diethanamine-tethered analog 1.

Synthesis, crystal structures and DNA-cleaving activities of [Cemp]2[MCl4] (Cemp = N-carbethoxymethyl-1,10-phenanthrolinium, M = Cu(II), Zn(II), Co(II), Ni(II) and Mn(II)).

N-Carbethoxymethyl-1,10-phenanthrolinium bromide (CempBr) and its five ionic metal complexes, [Cemp]2[MCl4] where M = Cu(II) (1), Zn(II) (2), Co(II) (3), Ni(II) (4) and Mn(II) (5) were synthesized and fully characterized. Complexes 1-5 have similar structures, and consist of isolated [Cemp](+) cations and [MCl4](2-) anions in which there are no obvious interactions between the oxygen or nitrogen donor atoms in [Cemp](+) and the metal center in [MCl4](2-). Agarose gel electrophoresis studies on the cleavage of plasmid pBR322 DNA by complexes 1-5 indicated that complex 1 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanism.

Synthesis, characterization and potent DNA-cleaving activity of copper(II)-complexed berberine carboxylate.

9-O-(4-carboxybenzyl)berberine (CBB) 1 was synthesized from the reaction of berberrubine with methyl 4-(bromomethyl)benzoate and subsequent hydrolysis. Its Cu(II) complex 2 was prepared from the reaction with Cu(NO(3))(2)·3H(2)O, and established as [Cu(CBB)(2)](NO(3))(2)·2H(2)O by means of (1)H NMR, UV, IR, elemental analysis and TGA measurements. Agarose gel electrophoresis study on the cleavage of plasmid pBR322 DNA indicated that complex 2 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanistic pathway involving the formation of singlet oxygen as the reactive species.

Facile synthesis of a dimeric dipyrrole-polyamide and synergetic DNA-cleaving activity of its Cu(II) complex.

Inspired by the potent DNA-cleaving activity of the Cu(II) complex of monopyrrole-polyamide dimer 1 (i.e., 1@Cu(2+)), we designed a new dimeric dipyrrole-polyamide analog 2 with the aim to optimize the catalytic activities of the metal complexes of this type of polypyrrole-polyamides.

Synergetic DNA-cleaving activities of the metal complexes of a polyether-tethered pyrrole-polyamide dimer.

A simple polyether-tethered pyrrole-polyamide dimer 1 was synthesized in 50% yield from the reaction of 2,2,2-trichloro-1-(1-methyl-4-nitro-1H-pyrrol-2-yl)ethanone with 2,2'-[1,2-ethanediylbis(oxy)]bisethanamine, and fully characterized on the basis of ¹H- and ¹³C-NMR, MS, HR-MS, and IR data. Agarose gel-electrophoresis study of the cleavage of plasmid pBR322 DNA by the complexes of compound 1 with seven metal ions indicated that most of the metal complexes were capable of efficiently cleaving DNA at pH 7.0 and 37°.

Synthesis, cytotoxicities and DNA-binding affinities of benzofuran-3-ols and their fused analogs.

A series of benzofuropyrazoles 2a-i were synthesized in 10-92% from the reaction of 2-aroylbenzofuran-3-ols 1a-i with hydrazine hydrate, and screened for their antitumor activities toward four human solid tumor cell lines, including gastric carcinoma cells MKN45, hepatocellular carcinoma cells HepG2, breast cancer cells MCF-7, and lung cancer cells A549. The results indicated that both compounds 1a-i and 2a-i displayed moderate antitumor activities. Among them, compound 2e exhibited potent inhibitory activity toward all the four tumor cell lines.

Simultaneous removing SO2 and NO by a new system containing cobalt complex.

Absorption and catalytic oxidation of nitric oxide can be achieved by using cobalt(III) ethylenediamine (Co(en)2(3+)). When simultaneous absorbing SO2 and NO, the precipitation of Co2(SO3)3 will be yielded and the NO removal will be decreased. A new catalyst system using Co(en)3(3+) coupled with urea has been developed to simultaneous remove NO and SO2 in the flue gas.