4 research outputs found

    Ametoctradin is a Potent <i>Q</i><sub>o</sub> Site Inhibitor of the Mitochondrial Respiration Complex III

    No full text
    Ametoctradin is a new <i>Oomycete</i>-specific fungicide under development by BASF. It is a potent inhibitor of the <i>bc</i><sub>1</sub> complex in mitochondrial respiration. However, its detailed action mechanism remains unknown. In the present work, the binding mode of ametoctradin was first uncovered by integrating molecular docking, MD simulations, and MM/PBSA calculations, which showed that ametoctradin should be a <i>Q</i><sub>o</sub> site inhibitor of <i>bc</i><sub>1</sub> complex. Subsequently, a series of new 1,2,4-triazolo­[1,5-<i>a</i>]­pyrimidine derivatives were designed and synthesized to further understand the substituent effects on the 5- and 6-position of 1,2,4-triazolo­[1,5-<i>a</i>]­pyrimidine. The calculated binding free energies (Δ<i>G</i><sub>cal</sub>) of newly synthesized analogues as <i>Q</i><sub>o</sub> site inhibitors correlated very well (<i>R</i><sup>2</sup> = 0.96) with their experimental binding free energies (Δ<i>G</i><sub>exp</sub>). Two compounds (<b>4a</b> and <b>4c</b>) with higher inhibitory activity against porcine SQR than ametoctradin were successfully identified. The structural and mechanistic insights obtained from the present study will provide a valuable clue for future designing of a new promising <i>bc</i><sub>1</sub> inhibitor

    InBr<sub>3</sub>‑Mediated One-Pot Synthesis of 2‑(Polyhydroxylatedalkyl)‑<i>N</i>‑aryl-/-alkylpyrroles from 1,2-Cyclopropa-3-pyranone and Amines

    No full text
    An efficient one-pot synthesis of polyhydroxyalkyl-substituted pyrroles from 1,2-cyclopropa-3-pyranones with primary amines is reported. With 10% of InBr<sub>3</sub> as the catalyst, both aryl- and alkylamines as well as various 1,2-cyclopropa-3-pyranones are well tolerated. This method is highly appealing because of its one-pot process, mild reaction conditions, substrate simplicity, and broad substrate scope

    Graphene Oxide Signal Reporter Based Multifunctional Immunosensing Platform for Amperometric Profiling of Multiple Cytokines in Serum

    No full text
    Cytokines are small proteins and form complicated cytokine networks to report the status of our health. Thus, accurate profiling and sensitive quantification of multiple cytokines is essential to have a comprehensive and accurate understanding of the complex physiological and pathological conditions in the body. In this study, we demonstrated a robust electrochemical immunosensor for the simultaneous detection of three cytokines IL-6, IL-1β, and TNF-α. First, graphene oxides (GO) were loaded with redox probes nile blue (NB), methyl blue (MB), and ferrocene (Fc), followed by covalent attachment of anti-cytokine antibodies for IL-6, IL-1β, and TNF-α, respectively, to obtain Ab<sub>2</sub>-GO-NB, Ab<sub>2</sub>-GO-MB, and Ab<sub>2</sub>-GO-Fc, acting as the signal reporters. The sensing interface was fabricated by attachment of mixed layers of 4-carboxylic phenyl and 4-aminophenyl phosphorylcholine (PPC) to glassy carbon surfaces. After that, the capture monoclonal antibody for IL-6, IL-1β, and TNF-α was modified to the carboxylic acid terminated sensing interface. And finally a sandwich assay was developed. The quantitative detection of three cytokines was achieved by observing the change in electrochemical signal from signal reporters Ab<sub>2</sub>-GO-NB, Ab<sub>2</sub>-GO-MB, and Ab<sub>2</sub>-GO-Fc. The designed system has been successfully used for detection of three cytokines (IL-6, IL-1β, and TNF-α) simultaneously with desirable performance in sensitivity, selectivity, and stability, and recovery of 93.6%–105.5% was achieved for determining cytokines spiked in the whole mouse serum

    pH-Responsive Surface Activity and Solubilization with Novel Pyrrolidone-Based Gemini Surfactants

    No full text
    A new series of pH-responsive Gemini surfactants with 2-pyrrolidone head groups, <i><i>N,N</i></i>′-dialkyl-<i><i>N,N</i></i>′-di­(ethyl-2-pyrrolidone)­ethylenediamine (Di-C<sub><i>n</i></sub>P, where <i>n</i> = 6, 8 10, 12), were synthesized and characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, ESI-MS, and elemental analysis. The surface activity and micellization behavior at acidic, neutral, and basic conditions were characterized by equilibrium surface tension and fluorescence techniques. It was found that the surface activity of Di-C<sub><i>n</i></sub>P depends on the pH of aqueous solutions due to the protonation state of surfactant molecules when pH was varied. The new compounds have lower cmc and γ<sub>cmc</sub> in comparison with that of <i>m</i>-2-<i>m</i> type conventional cationic Gemini surfactants and gluconamide-type nonionic Gemini surfactants. Fluorescence data confirm that micelles are formed when the concentration is above the cmc. Since micellization is of fundamental importance in surfactant applications such as solubilization, microemulsion, and related technologies, the significant difference in cmc at different pH of this new Gemini surfactant is employed to solubilize cyclohexane. The preliminary result indeed shows that the solubilization capacity of Di-C<sub><i>n</i></sub>P can be tuned by pH
    corecore