Design, Synthesis, and Anti-SARS-CoV-2 Activity of Amodiaquine Analogs.

The pandemic of coronavirus disease 2019, caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a serious concern worldwide. Although some effective vaccines have been developed, only a few anti-SARS-CoV-2 drugs have been approved for their clinical use. In this study, we designed and synthesized new anti-SARS-CoV-2 drugs based on the chemical structure of amodiaquine, which is known as an antimalarial drug.

Synthesis and isolation of metalloprotein on a super water-repellent umbrella-shaped pillar array with double re-entrant structure.

This paper reports the generation of microdroplets on a water-repellent device equipped with an array of tiny umbrella-shaped pillar structures. The microdroplets were used for chemical synthesis, docking, and crystallization of a functional protein. The umbrella-shaped water-repellent devices were easily fabricated from SU-8 by soft micro-electromechanical systems technology, which would suit mass production.

Synthesis of new functionalized bioactive S-substituted indolyl-triazoles as cytotoxic and apoptotic agents through multi-targeted kinase inhibition.

The search for new anticancer compounds is a major focus for researchers in chemistry, biology, and medicine. Cancer affects people of all ages and regions, with rising incidence rates. It does not discriminate by age or gender, making it a significant threat to humanity.

Amodiaquine Analogs Are Potent Inhibitors of Interleukin-6 Production Induced by Activation of Toll-Like Receptors Recognizing Pathogen Nucleic Acids.

Excessive inflammatory responses to viral infections, known as cytokine storms, are caused by overactivation of endolysosomal Toll-like receptors (TLRs) (TLR3, TLR7, TLR8, and TLR9) and can be lethal, but no specific treatment is available. Some quinoline derivatives with antiviral activity were tried during the recent coronavirus disease 2019 (COVID-19) pandemic, but showed serious toxicity, and their efficacy for treating viral cytokine storms was not established. Here, in order to discover a low-toxicity quinoline derivative as a candidate for controlling virally induced inflammation, we synthesized a series of derivatives of amodiaquine (ADQ), a quinoline approved as an antimalarial, and tested their effects on TLRs-mediated production of inflammatory cytokines and cell viability in vitro.

Induction of Paraptotic Cell Death in Cancer Cells by Triptycene-Peptide Hybrids and the Revised Mechanism of Paraptosis II.

In previous work, we reported on iridium(III) (Ir(III)) complex-peptide hybrids as amphiphilic conjugates (IPH-ACs) and triptycene-peptide hybrids as amphiphilic conjugates (TPH-ACs) and found that these hybrid compounds containing three cationic KK(K)GG peptide units through C-C alkyl linkers induce paraptosis II, which is one of the nonapoptotic programmed cell death (PCD) types in Jurkat cells and different from previously reported paraptosis. The details of that study revealed that the paraptosis II induced by IPH-ACs (and TPH-ACs) proceeds via a membrane fusion or tethering of the endoplasmic reticulum (ER) and mitochondria, and Ca transfer from the ER to mitochondria, which results in a loss of mitochondrial membrane potential () in Jurkat cells. However, the detailed mechanistic studies of paraptosis II have been conducted only in Jurkat cells.

Optical Resolution of Carboxylic Acid Derivatives of Homoleptic Cyclometalated Iridium(III) Complexes via Diastereomers Formed with Chiral Auxiliaries.

We report on a facile method for the optical resolution of cyclometalated iridium(III) (Ir(III)) complexes via diastereomers formed with chiral auxiliaries. The racemic carboxylic acids of Ir(III) complexes (- (-Ir(ppyCOH) (ppy: 2-phenylpyridine)), - (-Ir(tpyCOH) (tpy: 2-(4'-tolyl)pyridine)), and - (-Ir(mpiqCOH) (mpiq: 1-(4'-methylphenyl)isoquinoline))) were converted into the diastereomers, Δ- and Λ-forms of - (from -), - (from -), - (from -), and - (from -), respectively, by the condensation with (12)-1,2-diaminocyclohexane or (12)-2-aminocyclohexanol. The resulting diastereomers were separated by HPLC (with a nonchiral column) or silica gel column chromatography, and their absolute stereochemistry was determined by X-ray single-crystal structure analysis and CD (circular dichroism) spectra.

Development of Wireless Power-Transmission-Based Photodynamic Therapy for the Induction of Cell Death in Cancer Cells by Cyclometalated Iridium(III) Complexes.

Photodynamic therapy (PDT), a noninvasive method for cancer therapy, involves the generation of reactive oxygen species (ROS) by the photochemical excitation of photosensitizers (PSs) to induce cell death in cancer cells. A variety of PS including porphyrin derivatives and metal complexes such as iridium (Ir) complexes have been reported. In clinical trials, red-near infrared (NIR) light (650-900 nm) is preferred for the excitation of PSs due to its deeper penetration into tissues compared with visible light (400-500 nm).

Enhanced Photocatalytic Degradation Activity Using the VO/RGO Composite.

Semiconductor-based photocatalyst materials played an important role in the degradation of organic compounds in recent years. Photocatalysis is a simple, cost-effective, and environmentally friendly process for degrading organic compounds. In this work, vanadium pentoxide (VO) and VO/RGO (reduced graphene oxide) composite were synthesized by a hydrothermal method.

Investigation of bactericidal effect of a mid-infrared free electron laser on Escherichia coli.

The rapid increase in the number of bacteria that are resistant to many commonly used antimicrobial agents and their global spread have become a major problem worldwide. In particular, for periodontal disease, which is a localized infection, there is a growing need for treatment methods that do not primarily involve antimicrobial agents, and antimicrobial photodynamic therapy (aPDT) is attracting attention. In this study, the bactericidal effects of a mid-infrared free electron laser (MIR-FEL) on E.

Profiling Differential Effects of 5 Selective Serotonin Reuptake Inhibitors on TLRs-Dependent and -Independent IL-6 Production in Immune Cells Identifies Fluoxetine as Preferred Anti-Inflammatory Drug Candidate.

Excessive proinflammatory cytokine production induced by abnormal activation of Toll-like receptor (TLR) signaling, for example, by SARS-CoV-2 infection, can cause a fatal cytokine storm. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine, used to treat depression, were recently reported to reduce the risk of severe disease in patients with coronavirus disease 2019 (COVID-19), but the mechanisms of the anti-inflammatory effects of SSRIs, and which SSRI would be most suitable as an anti-inflammatory drug, remain unclear. Here, we examined the inhibitory effects of 5 FDA-approved SSRIs, paroxetine, fluoxetine, fluvoxamine, sertraline and escitalopram, on the production of interleukin-6 (IL-6) induced by stimulation with multiple TLR agonists in murine macrophages and dendritic cells, and on the production of cytokines induced by concanavalin A in murine lymphocytes.

Design, Synthesis, and Anticancer Activity of Triptycene-Peptide Hybrids that Induce Paraptotic Cell Death in Cancer Cells.

We report on the design and synthesis of triptycene-peptide hybrids (TPHs), , -, and -, which are conjugates of a triptycene core unit with two or three cationic KKKGG peptides (K: lysine and G: glycine) through a C alkyl chain. It was discovered that - and - induce paraptosis, a type of programmed cell death (PCD), in Jurkat cells (leukemia T-lymphocytes). Mechanistic studies indicate that these TPHs induce the transfer of Ca from the endoplasmic reticulum (ER) to mitochondria, a loss of mitochondrial membrane potential (ΔΨ), tethering of the ER and mitochondria, and cytoplasmic vacuolization in the paraptosis processes.

Cyclometalated Iridium(III) Complex-Cationic Peptide Hybrids Trigger Paraptosis in Cancer Cells via an Intracellular Ca Overload from the Endoplasmic Reticulum and a Decrease in Mitochondrial Membrane Potential.

In our previous paper, we reported that amphiphilic Ir complex-peptide hybrids (IPHs) containing basic peptides such as KK(K)GG (K: lysine, G: glycine) (e.g., ASb-2) exhibited potent anticancer activity against Jurkat cells, with the dead cells showing a strong green emission.

Visible light activation of photocatalysts formed from the heterojunction of sludge-generated TiO and g-CN towards NO removal.

The feasibility of preparing TiO/g-CN heterojunction from Ti-incorporated dried dye wastewater sludge is explored in this study. Two reaction routes of composite formation were evaluated. In the initial approach, one-step calcination of dried sludge and melamine mixture @600 °C was carried out.

Spontaneous deformation and fission of oil droplets on an aqueous surfactant solution.

We investigated the spontaneous deformation and fission of a tetradecane droplet containing palmitic acid (PA) on a stearyltrimethylammonium chloride (STAC) aqueous solution. In this system, the generation and rupture of the gel layer composed of PA and STAC induce the droplet deformation and fission. To investigate the characteristics of the droplet-fission dynamics, we obtained the time series of the number of the droplets produced by fission and confirmed that the number has a peak at a certain STAC concentration.

Development of dark-field dynamic light scattering microscopy and its application: Tracking dynamics of particles in condensed slurries spreading on planar/nonplanar substrates.

Hypothesis: While dynamics of particles in slurries is usually evaluated by dynamic light scattering measurements, this technique had only been applicable to particles in the bulk slurries. Because this limitation is mainly owing to strong reflection of light, the dynamics of particles in slurries spreading/drying on solid substrates is to be obtained by spatially separating the reflection light from scattering (signal) light. This may allow us to track the particles in practical samples such as cosmetics or inks spreading on solid surfaces.

Amphiphilic Cationic Triscyclometalated Iridium(III) Complex-Peptide Hybrids Induce Paraptosis-like Cell Death of Cancer Cells via an Intracellular Ca-Dependent Pathway.

We report on the design and synthesis of a green-emitting iridium complex-peptide hybrid (IPH) , which has an electron-donating hydroxyacetic acid (glycolic acid) moiety between the Ir core and the peptide part. It was found that is selectively cytotoxic against cancer cells, and the dead cells showed a green emission. Mechanistic studies of cell death indicate that induces a paraptosis-like cell death through the increase in mitochondrial Ca concentrations via direct Ca transfer from ER to mitochondria, the loss of mitochondrial membrane potential (ΔΨ), and the vacuolization of cytoplasm and intracellular organelle.

Stabilization of indocyanine green dye in polymeric micelles for NIR-II fluorescence imaging and cancer treatment.

One of the most commonly used near infrared (NIR) dyes is indocyanine green (ICG), which has been extensively used for NIR bioimaging, photothermal and photodynamic therapy. However, upon excitation this dye can react with molecular oxygen to form singlet oxygen (SO), which can then cleave ICG to form non-fluorescent debris. In order to reduce the reaction between ICG and oxygen, we used energy transfer (ET) between the former and the NIR dye IR-1061.

Enhancement of Meniscus Pump by Multiple Particles.

We numerically investigate the behavior of a droplet spreading on a smooth substrate with multiple obstacles. As experimental works have indicated, the macroscopic contact line or the three-phase boundary line of a droplet exhibits significant deformation resulting in a local acceleration by successive interactions with an array of tiny obstacles settled on the substrate (Mu et al., ).

Pumping effect of heterogeneous meniscus formed around spherical particle.

Hypothesis: A disturbance such as a microparticle on the pathway of a spreading droplet has shown the tremendous ability to accelerate locally the motion of the macroscopic contact line (Mu et al., 2017). Although this ability has been linked to the particle-liquid interaction, the physical mechanisms behind it are still poorly understood despite its academic interest and the scope of numerous industrial applications in need of fast wetting.

Biological Deep Temperature Imaging with Fluorescence Lifetime of Rare-Earth-Doped Ceramics Particles in the Second NIR Biological Window.

Contactless thermal imaging generally relies on mid-infrared cameras and fluorescence imaging with temperature-sensitive phosphors. Fluorescent thermometry in the near-infrared (NIR) region is an emerging technique for analysing deep biological tissues but still requires observation depth calibration. We present an NIR fluorescence time-gated imaging (TGI) thermometry technology based on fluorescence lifetime, an intrinsic fluorophore time constant unrelated to observation depth.

Rapid increase in transparency of biological organs by matching refractive index of medium to cell membrane using phosphoric acid.

Tissue clearing is a fundamental challenge in biology and medicine to achieve high-resolution optical imaging of tissues deep inside intact organs. The clearing methods reported up to now require long incubation times or physical/electrical pressure to achieve tissue clearing, which is done by matching the refractive indices of the whole sample and medium to that of the lipid layer. Here we show that phosphoric acid increases the refractive index of the medium and can increase the transparency of formalin-fixed tissue samples rapidly.

Delayed Increase in Near-Infrared Fluorescence in Cultured Murine Cancer Cells Labeled with Oxygen-Doped Single-Walled Carbon Nanotubes.

The labeling technique for cells with over-thousand-nanometer near-infrared (OTN-NIR) fluorescent probes has attracted much attention for in vivo deep imaging for cell tracking and cancer metastasis, because of low scattering and absorption of OTN-NIR light by biological tissues. However, the intracellular behavior following the uptake of the single-walled carbon nanotubes (SWCNTs), an OTN-NIR fluorophore, remains unknown. The aim of this study is to investigate the time-dependent change in OTN-NIR fluorescence images of cultured murine cancer cells (Colon-26) following treatment with a recently developed OTN-NIR fluorescent probe, epoxide-type oxygen-doped SWCNTs (o-SWCNTs).

Temperature Sensing of Deep Abdominal Region in Mice by Using Over-1000 nm Near-Infrared Luminescence of Rare-Earth-Doped NaYF Nanothermometer.

Luminescence nanothermometry has attracted much attention as a non-contact thermal sensing technique. However, it is not widely explored for in vivo applications owing to the low transparency of tissues for the light to be used. In this study, we performed biological temperature sensing in deep tissues using β-NaYF nanoparticles co-doped with Yb, Ho, and Er (NaYF: Yb, Ho, Er NPs), which displayed two emission peaks at 1150 nm (Ho) and 1550 nm (Er) in the >1000 nm near-infrared wavelength region, where the scattering and absorption of light by biological tissues are at the minimum.

Synthesis of 2,2-Dialkyl Chromanes by Intramolecular Ullmann C-O Coupling Reactions toward the Total Synthesis of D-α-Tocopherol.

The complete synthesis of D-α-tocopherol was achieved using our developed-Ullmann C-O coupling reaction as a key reaction. The synthesis of the core structure of D-α-tocopherol, which is a chiral chromane, has never been reported using intramolecular Ullmann C-O coupling reactions owing to the low reactivity of electron-rich iodoarenes with tertiary alcohols. Because the developed intramolecular C-O coupling reactions prefer electron-rich iodoarenes with tertiary alcohols, we successfully synthesized the chiral chromane core and achieved the total synthesis of D-α-tocopherol.