The indiscriminate use of antibiotics brings an alarming reality: in 2050, bacterial resistance could be the main cause of death in the world, resulting in the death of 10 million people, according ...to the World Health Organization (WHO). In this sense, to combat bacterial resistance, several natural substances, including chalcones, have been described in relation to antibacterial, representing a potential tool for the discovery of new antibacterial drugs.
The objective of this study is to perform a bibliographic survey and discuss the main contributions in the literature about the antibacterial potential of chalcones in the last 5 years.
A search was carried out in the main repositories, for which the publications of the last 5 years were investigated and discussed. Unprecedented in this review, in addition to the bibliographic survey, molecular docking studies were carried out to exemplify the applicability of using one of the molecular targets for the design of new entities with antibacterial activity.
In the last 5 years, antibacterial activities were reported for several types of chalcones, for which activities were observed for both gram-positive and gram-negative bacteria with high potency, including MIC values in the nanomolar range. Molecular docking simulations demonstrated important intermolecular interactions between chalcones and residues from the enzymatic cavity of the enzyme DNA gyrase, one of the validated molecular targets in the development of new antibacterial agents.
The data presented demonstrate the potential of using chalcones in drug development programs with antibacterial properties, which may be useful to combat resistance, a worldwide public health problem.
In the Mekong River delta and its associated coastal zone trace elements concentrations (Cd, Cu, Ni and Pb) were measured in the dissolved phase (DP) during dry (March 1997) and wet (October 1997) ...seasons. As, Co, Cr, Ni, Pb, and Al were also measured in suspended matter (SM) and total and organic carbon, trace elements (Cd, Cr, Cu, Hg, Mn, Ni, Pb, Zn) and macro elements in superficial sediments (S). Trace metal concentrations in DP and SM during the contrasting hydrological conditions were generally found within the range observed for uncontaminated environment. The average DP concentrations (nM) in the river for March and October are: Cd 0.03 and 0.09, Cu 15 and 14, Ni 7.8 and 8.4, Pb 0.51 and 0.50, respectively. In general there is no significant difference between the concentrations observed during dry and wet season. The evolution of the DP trace metal concentration in the surface water within the salinity gradient suggests no noticeable exchange between the particulate and dissolved phase. This result is in good agreement with those observed in most plume structures studied so far. The average concentrations in the SM (μg/g) (March, October) at the river end-member are: As (24; 11), Co (17; 9), Cr (49; 29), Ni (32; 18), Pb (42; 19) and Al (113
000; 67
000), respectively. All trace elements show higher concentrations in March than in October, with an average increase of two times. This is essentially related to grain size effect since smaller particles were supplied during dry season. These differences are not reflected in the mixing zone, which integrates the seasonal variations. The concentration of major elements (C total, C organic, Si, Al, Ca, K, Fe, Mg, Ti), trace elements (Pb, Zn, Cu, Ni, Mn, Cr, Cd, Hg) in superficial sediments, show similar values during the two seasons and does not show any important variation with depth, indicating either a very fast sedimentation rate and/or the absence of any significant contamination.
Leishmaniasis is a group of neglected tropical diseases whose treatment with antimonials bears limitations and has changed little in over 80 years. Medicinal plants have been evaluated as a ...therapeutic alternative for leishmaniasis. Arrabidaea chica is popularly used as a wound healing and antiparasitic agent, especially as leishmanicidal agent. This study examined the leishmanicidal activity of a crude extract (ACCE), an anthocyanidin-rich fraction (ACAF), and three isolated anthocyanidins from A. chica: carajurin, 3′-hydroxy-carajurone, and carajurone. We evaluated the antileishmanial activity against promastigote and intracellular amastigote forms of Leishmania amazonensis and determined cytotoxicity in BALB/c peritoneal macrophages, as well as nitrite quantification, using the Griess method. Molecular docking was carried out to evaluate interactions of carajurin at the nitric oxide synthase enzyme. All compounds were active against promastigotes after 72 h, with IC50 values of 101.5 ± 0.06 μg/mL for ACCE and 4.976 ± 1.09 μg/mL for ACAF. Anthocyanidins carajurin, 3′-hydroxy-carajurone, and carajurone had IC50 values of 3.66 ± 1.16, 22.70 ± 1.20, and 28.28 ± 0.07 μg/mL, respectively. The cytotoxicity assay after 72 h showed results ranging from 9.640 to 66.74 µg/mL for anthocyanidins. ACAF and carajurin showed selectivity against intracellular amastigote forms (SI> 10), with low cytotoxicity within 24 h, a statistically significant reduction in all infection parameters, and induced nitrite production. Molecular docking studies were developed to understand a possible mechanism of activation of the nitric oxide synthase enzyme, which leads to an increase in the production of nitric oxide observed in the other experiments reported. These results encourage us to suggest carajurin as a biological marker of A. chica.
Display omitted
•Carajurin is the major anthocyanidin compound of A. chica.•Anthocyanidins are active against promastigote forms of L. amazonensis.•Carajurin is active against intracellular amastigote forms of L. amazonensis.•Carajurin increases nitrite levels in unstimulated or stimulated cells.•Carajurin interacts at the activation site of nitrous oxide synthase.
The goal of the INFN-RETINA R&D project is to develop and implement a computational methodology that allows to reconstruct events with a large number (> 100) of charged-particle tracks in pixel and ...silicon strip detectors at 40 MHz, thus matching the requirements for processing LHC events at the full bunch-crossing frequency. Our approach relies on a parallel pattern-recognition algorithm, dubbed artificial retina, inspired by the early stages of image processing by the brain. In order to demonstrate that a track-processing system based on this algorithm is feasible, we built a sizable prototype of a tracking processor tuned to 3 000 patterns, based on already existing readout boards equipped with Altera Stratix III FPGAs. The detailed geometry and charged-particle activity of a large tracking detector currently in operation are used to assess its performances. We report on the test results with such a prototype.
We present the latest results of an R&D study for a specialized processor capable of reconstructing, in a silicon pixel detector, high-quality tracks from high-energy collision events at 40MHz. The ...processor applies a highly parallel pattern-recognition algorithm inspired to quick detection of edges in mammals visual cortex. After a detailed study of a real-detector application, demonstrating that online reconstruction of offline-quality tracks is feasible at 40MHz with sub-microsecond latency, we are implementing a prototype using common high-bandwidth FPGA devices.
Chagas Disease is caused by the protozoan Trypanosoma cruzi and is considered a tropical neglected disease by the World Health Organization (WHO). The main drugs used in the therapy of the disease ...are obsolete and, as a result, it still kills millions of people every year. Therefore, the development of new drugs is urgent, as is the research reported in this article, in which new triazole selenides were synthesized through a simple methodology and to evaluate their potential against T. cruzi, through a combination of in vitro and in silico assays. With the combination of two molecular scaffolds already known for this activity, sixteen new hybrid compounds were obtained, showing yields ranging from 40 to 90%, and their biological potentials were tested. Two of the evaluated hybrids showed potent trypanocidal activity (11m and 11n), comparable to the positive control benznidazole. Density functional theory (DFT) studies were correlated with cyclic voltammetry assays to investigate the LUMO energy, which demonstrated a correlation with the observed trypanocidal activity. These results are promising, considering 11m and 11n as hit compounds in the development of new antichagasic drugs.
Display omitted
•New 1,2,3-triazole-chalcogen hybrids were synthesized.•The hybrids were evaluated against T. cruzi, through a combination of in vitro and in silico assays.•The trypanocide assays revealed two promising compounds, 11m and 11n.•DFT and CV studies demonstrated a correlation with trypanocidal activity observed.•11m-n represent promising hit compounds in the discovery of new antichagasic drugs.
Display omitted
Using proton-proton collision data at centre-of-mass energies of s=7,8 and 13TeV recorded by the LHCb experiment at the Large Hadron Collider, corresponding to an integrated ...luminosity of 9fb-1, the invariant mass spectrum of J/ψ pairs is studied. A narrow structure around 6.9GeV/c2 matching the lineshape of a resonance and a broad structure just above twice the J/ψ mass are observed. The deviation of the data from nonresonant J/ψ-pair production is above five standard deviations in the mass region between 6.2 and 7.4GeV/c2, covering predicted masses of states composed of four charm quarks. The mass and natural width of the narrow X(6900) structure are measured assuming a Breit-Wigner lineshape.
A test of lepton universality, performed by measuring the ratio of the branching fractions of the $B^0 → K^{*0}μ^+μ^-$ and $B^0$ → $K^{*0}e^+e^-$ decays, $R_{K^{*0}}$, is presented. The $K^{*0}$ ...meson is reconstructed in the final state $K^+π^-$, which is required to have an invariant mass within 100 MeV/c2 of the known $K^*$ (892)0 mass. The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of about 3 fb-1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The ratio is measured in two regions of the dilepton invariant mass squared, q2, to be R K ∗ 0 = { 0.66 − + 0.07 0.11 ( s t a t ) ± 0.03 ( s y s t ) f o r 0.045 < q 2 < 1.1 G e V 2 / c 4 , 0.69 − + 0.07 0.11 ( s t a t ) ± 0.05 ( s y s t ) f o r 1.1 < q 2 < 6.0 G e V 2 / c 4 . The corresponding 95.4% confidence level intervals are 0.52, 0.89 and 0.53, 0.94. The results, which represent the most precise measurements of $R_{K^{*0}}$ to date, are compatible with the Standard Model expectations at the level of 2.1–2.3 and 2.4–2.5 standard deviations in the two q2 regions, respectively.
Alzheimer's disease (AD) is a neurodegenerative disease that is characterized as the main dementia in the elderly. Eighteen pyrazolines were synthesized and evaluated for their inhibitory effects ...against acetylcholinesterase (AChE)
in vitro
. Possible interactions between pyrazolines and the enzyme were explored by
in silico
experiments. Compound
2B
of the series was the most active pyrazoline with an IC
50
value of 58 nM. Molecular docking studies revealed two important π-π interactions with residues Trp 286 and Tyr 341. A correlation between the HOMO-1 surface and AChE inhibition was observed. ADMET assays demonstrated a good profile for compound
2B
. From the abovementioned findings, a new avenue of compound
2B
analogues could be explored to develop anti-AD agents.
We report the synthesis and investigation of the anticholinesterase potential of pyrazolines, using experimental and theoretical techniques.
PDF
