Quinazolinone-based rhodanine-3-acetic acids as potent aldose reductase inhibitors: Synthesis, functional evaluation and molecular modeling study

A series of quinazolinone-based rhodanine-3-acetic acids was synthesized and tested for in vitro aldose reductase inhibitory activity. All the target compounds displayed nanomolar activity against the target enzyme. Compounds 3a, 3b, and 3e exhibited almost 3-fold higher activity as compared to the only marketed reference drug epalrestat. Structure-activity relationship studies indicated that bulky substituents at the 3-phenyl ring of the quinazolinone moiety are generally not tolerated in the active site of the enzyme. Insertion of a methoxy group on the central benzylidene ring was found to have a variable effect on ALR-2 activity depending on the nature of peripheral quinazolinone ring substituents. Removal of the acetic acid moiety led to inactive or weakly active target compounds. Docking and molecular dynamic simulations of the most active rhodanine-3-acetic acid derivatives were also carried out, to provide the basis for further structure-guided design of novel inhibitors

Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against Clostridium difficileof novel 3-biaryl-N-benzylpropan-1-amine derivatives

The synthesis of a series of benzimidazole-N-benzylpropan-1-amines and adenine-N-benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium Clostridium difficile was performed with three amine derivatives displaying MIC values of 16 μg/mL. Molecular docking studies of the described amines determined that the amines interact within two active site pockets of C. difficile methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interaction

Perspective Chapter: The Toxic Silver (Hg)

In the late 1950s, residents of a Japanese fishing village known as “Minamata” began falling ill and dying at an alarming rate. The Japanese authorities stated that methyl-mercury-rich seafood and shellfish caused the sickness. Burning fossil fuels represent ≈52.7% of Hg emissions. The majorities of mercury’s compounds are volatile and thus travel hundreds of miles with wind before being deposited on the earth’s surface. High acidity and dissolved organic carbon increase Hg-mobility in soil to enter the food chain. Additionally, Hg is taken up by areal plant parts via gas exchange. Mercury has no identified role in plants while exhibiting high affinity to form complexes with soft ligands such as sulfur and this consequently inactivates amino acids and sulfur-containing antioxidants. Long-term human exposure to Hg leads to neurotoxicity in children and adults, immunological, cardiac, and motor reproductive and genetic disorders. Accordingly, remediating contaminated soils has become an obligation. Mercury, like other potentially toxic elements, is not biodegradable, and therefore, its remediation should encompass either removal of Hg from soils or even its immobilization. This chapter discusses Hg’s chemical behavior, sources, health dangers, and soil remediation methods to lower Hg levels

MUSiC: a model-unspecific search for new physics in proton–proton collisions at √s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton–proton collision data recorded at the LHC at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 35.9fb-1, are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches

Observation of the Bc+_\mathrm{c}^+ Meson in Pb-Pb and pp Collisions at sNN\sqrt{s_{\mathrm{NN}}} = 5.02 TeV and Measurement of its Nuclear Modification Factor

The B$_\mathrm{c}^+$ meson is observed for the first time in heavy ion collisions. Data from the CMS detector are used to study the production of the B$_\mathrm{c}^+$ meson in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV , via the B$_\mathrm{c}^+$ → (J/ψ → μ$^+$μ$^−$)μ$^+$ν$_μ$ decay. The B$_\mathrm{c}^+$ nuclear modification factor, derived from the PbPb-to-pp ratio of production cross sections, is measured in two bins of the trimuon transverse momentum and of the PbPb collision centrality. The B$_\mathrm{c}^+$meson is shown to be less suppressed than quarkonia and most of the open heavy-flavor mesons, suggesting that effects of the hot and dense nuclear matter created in heavy ion collisions contribute to its production. This measurement sets forth a promising new probe of the interplay of suppression and enhancement mechanisms in the production of heavy-flavor mesons in the quark-gluon plasma

Observation of Forward Neutron Multiplicity Dependence of Dimuon Acoplanarity in Ultraperipheral Pb-Pb Collisions at sNN\sqrt{sNN} =5.02 TeV

The first measurement of the dependence of γγ→μ$^{+}$ μ$^{-}$ production on the multiplicity of neutrons emitted very close to the beam direction in ultraperipheral heavy ion collisions is reported. Data for lead-lead interactions at $\sqrt{^{s}NN}$=5.02 TeV, with an integrated luminosity of approximately 1.5nb$^{-1}$, are collected using the CMS detector at the LHC. The azimuthal correlations between the two muons in the invariant mass region 88.3. The back-to-back correlation structure from leading-order photon-photon scattering is found to be significantly broader for events with a larger number of emitted neutrons from each nucleus, corresponding to interactions with a smaller impact parameter. This observation provides a data-driven demonstration that the average transverse momentum of photons emitted from relativistic heavy ions has an impact parameter dependence. These results provide new constraints on models of photon-induced interactions in ultraperipheral collisions. They also provide a baseline to search for possible final-state effects on lepton pairs caused by traversing a quark-gluon plasma produced in hadronic heavy ion collisions

Measurements of the differential cross sections of the production of Z + jets and γ + jets and of Z boson emission collinear with a jet in pp collisions at s \sqrt{s} = 13 TeV

Measurements of the differential cross sections of Z + jets and γ + jets production, and their ratio, are presented as a function of the boson transverse momentum. Measurements are also presented of the angular distribution between the Z boson and the closest jet. The analysis is based on pp collisions at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 35.9 fb−1 recorded by the CMS experiment at the LHC. The results, corrected for detector effects, are compared with various theoretical predictions. In general, the predictions at higher orders in perturbation theory show better agreement with the measurements. This work provides the first measurement of the ratio of the differential cross sections of Z + jets and γ + jets production at 13 TeV, as well as the first direct measurement of Z bosons emitted collinearly with a jet