The use of inhaled corticosteroid in preschool wheezers: what's the point today?

Among the preschool children who wheeze two different groups can be identify: children who have a viral infection and those who respond to multiple triggers, such as exercise or allergens

(2<i>R</i>, 4<i>S</i>, 5<i>S</i>) 1-(4-(4-(((7-Chloroquinolin-4-yl)amino)methyl)-1<i>H</i>-1,2,3-triazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1<i>H</i>,3<i>H</i>)-dione

1,2,3-triazole pharmacophore is a widely recognized motif used for a variety of applications, including drug discovery, chemical biology, and materials science. We herein report the synthesis of a derivative of azidothymidine (AZT), which was combined with the 7-chloro quinoline scaffold through a 1,4-disubstituted 1,2,3-triazole. The chemical structure of the new molecule was fully characterized by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC) distortionless enhancement by polarization transfer (DEPT), correlation spectroscopy (1H-1H-COSY), ultraviolet (UV) spectroscopy, and high-resolution mass spectrometry (HRMS). Computational studies were used to predict the interaction of the synthesized compound with HIV reverse transcriptase, a target of relevance for developing new therapeutics against AIDS. The drug-likeness of the compound was also investigated by computing the physico-chemical properties that are important for the pharmacokinetic profile

(2R,4aS,6aS,12bR,14aS,14bR)10-Hydroxy-<i>N</i>-(4-((6-methoxyquinolin-8-yl)amino)pentyl)-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide

We herein report the synthesis of a derivative of the natural compound celastrol linked to the antimalarial drug primaquine through an amide obtained by the activation of the carboxylic acid with HOBt/EDC. The chemical structure of the new molecule was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), heteronuclear single quantum coherence (HSQC), correlation spectroscopy (1H-1H-COSY), distortionless enhancement by polarization transfer (DEPT), mass spectrometry, Fourier-transform infrared (FTIR), and ultraviolet (UV) spectroscopies. Computational studies were enrolled to predict the interaction of the synthesized compound with sarco-endoplasmic reticulum (SR) Ca2+ transport ATPase (SERCA), a target of relevance for developing new therapeutics against arthritis. The drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties

4-(4-(((1<i>H</i>-Benzo[d][1,2,3]triazol-1-yl)oxy)methyl)-1<i>H</i>-1,2,3-triazol-1-yl)-7-chloroquinoline

The 1,2,3-triazole ring system can be easily obtained by widely used copper-catalyzed click reaction of azides with alkynes. 1,2,3-triazole exhibits myriad of biological activities, including antibacterial antimalarial, and antiviral activities. We herein reported the synthesis of quinoline-based [1,2,3]-triazole hybrid derivative via Cu(I)-catalyzed click reaction of 4-azido-7-chloroquinoline with alkyne derivative of hydroxybenzotriazole (HOBt). The compound was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), correlated spectroscopy (1H-1H-COSY), heteronuclear single quantum coherence (HSQC) and distortionless enhancement by polarization transfer (DEPT-135 and DEPT-90) NMR, ultraviolet (UV) and Fourier-transform infrared (FTIR) spectroscopies, and high-resolution mass spectrometry (HRMS). Computational studies were enrolled to predict the interaction of the synthesized compound with acetylcholinesterase, a target of primary relevance for developing new therapeutic options to counteract neurodegeneration. Moreover, the drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties

4-(4-(((1H-Benzo[d][1,2,3]triazol-1-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-7-chloroquinoline

The 1,2,3-triazole ring system can be easily obtained by widely used copper-catalyzed click reaction of azides with alkynes. 1,2,3-triazole exhibits myriad of biological activities, including antibacterial antimalarial, and antiviral activities. We herein reported the synthesis of quinoline-based [1,2,3]-triazole hybrid derivative via Cu(I)-catalyzed click reaction of 4-azido-7-chloroquinoline with alkyne derivative of hydroxybenzotriazole (HOBt). The compound was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), correlated spectroscopy (1H-1H-COSY), heteronuclear single quantum coherence (HSQC) and distortionless enhancement by polarization transfer (DEPT-135 and DEPT-90) NMR, ultraviolet (UV) and Fourier-transform infrared (FTIR) spectroscopies, and high-resolution mass spectrometry (HRMS). Computational studies were enrolled to predict the interaction of the synthesized compound with acetylcholinesterase, a target of primary relevance for developing new therapeutic options to counteract neurodegeneration. Moreover, the drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties

Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD)

The mechanism of host cell invasion of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 is connected with the interaction of spike protein (S) with angiotensin-converting enzyme 2 (ACE2) through receptor-binding domain (RBD). Small molecules targeting this assembly are being investigated as drug candidates to contrast SARS-CoV-2. In this context, chloroquine, an antimalarial agent proposed as a repurposed drug to treat coronavirus disease-19 (COVID-19), was hypothesized to bind RBD among its other mechanisms. Similarly, artemisinin and its derivatives are being studied as potential antiviral agents. In this work, we investigated the interaction of artemisinin, its metabolite dihydroartemisinin and chloroquine with RBD by means of computational tools and in vitro. Docking studies showed that the compounds interfere with the same region of the protein and molecular dynamics (MD) simulations demonstrated the stability of the predicted complexes. Bio-layer interferometry showed that chloroquine dose-dependently binds RBD (KD = 35.9 µM) more efficiently than artemisinins

Recurrent emergency department visits for asthma in children: an opportunity for asthma care improvement?

Examination of the relevance of emergency department visits as an opportunity to check the status of asthma treatment and follow-u

A Drug Repurposing Approach for Antimalarials Interfering with SARS-CoV-2 Spike Protein Receptor Binding Domain (RBD) and Human Angiotensin-Converting Enzyme 2 (ACE2)

Host cell invasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, computational and experimental techniques were combined to screen antimalarial compounds from different chemical classes, with the aim of identifying small molecules interfering with the RBD-ACE2 interaction and, consequently, with cell invasion. Docking studies showed that the compounds interfere with the same region of the RBD, but different interaction patterns were noted for ACE2. Virtual screening indicated pyronaridine as the most promising RBD and ACE2 ligand, and molecular dynamics simulations confirmed the stability of the predicted complex with the RBD. Bio-layer interferometry showed that artemisone and methylene blue have a strong binding affinity for RBD (KD = 0.363 and 0.226 μM). Pyronaridine also binds RBD and ACE2 in vitro (KD = 56.8 and 51.3 μM). Overall, these three compounds inhibit the binding of RBD to ACE2 in the μM range, supporting the in silico data