4 research outputs found
Ametoctradin is a Potent <i>Q</i><sub>o</sub> Site Inhibitor of the Mitochondrial Respiration Complex III
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-triazoloÂ[1,5-<i>a</i>]Âpyrimidine derivatives
were designed and synthesized to further understand the substituent
effects on the 5- and 6-position of 1,2,4-triazoloÂ[1,5-<i>a</i>]Âpyrimidine. 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
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
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
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>′-diÂ(ethyl-2-pyrrolidone)Âethylenediamine
(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