Development of an in Silico Model of DPPH• Free Radical Scavenging Capacity: Prediction of Antioxidant Activity of Coumarin Type Compounds.

A quantitative structure-activity relationship (QSAR) study of the 2,2-diphenyl-l-picrylhydrazyl (DPPH•) radical scavenging ability of 1373 chemical compounds, using DRAGON molecular descriptors (MD) and the neural network technique, a technique based on the multilayer multilayer perceptron (MLP), was developed. The built model demonstrated a satisfactory performance for the training ( R 2 = 0.713 ) and test set ( Q ext 2 = 0.654 ) , respectively. To gain greater insight on the relevance of the MD contained in the MLP model, sensitivity and principal component analyses were performed. Moreover, structural and mechanistic interpretation was carried out to comprehend the relationship of the variables in the model with the modeled property. The constructed MLP model was employed to predict the radical scavenging ability for a group of coumarin-type compounds. Finally, in order to validate the model's predictions, an in vitro assay for one of the compounds (4-hydroxycoumarin) was performed, showing a satisfactory proximity between the experimental and predicted pIC50 values.

Iodine(III)-Mediated Diazidation and Azido-oxyamination of Enamides.

In this study we demonstrate that the combination of bis(tert-butylcarbonyloxy)iodobenzene and lithium azide in acetonitrile allows the diazidation of various enamide substrates. The azido-oxyamination of the same substrates can be carried out in the presence of 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO). Control experiments strongly suggest that this latter process occurs through a shift in nature of the in situ generated electrophilic species from a radical to a cation. Finally, the versatility of the novel compounds synthesized was also assessed by running various selective reactions on them.

Development of 2-deoxystreptamine-nucleobase conjugates for the inhibition of oncogenic miRNA production.

The discovery of new original scaffolds for selective RNA targeting is one of the main challenges of current medicinal chemistry since therapeutically relevant RNAs represent potential targets for a number of pathologies. Recent efforts have been devoted to the search for RNA ligands targeting the biogenesis of oncogenic miRNAs whose overexpression has been directly linked to the development of various cancers. In this work, we developed a new series of RNA ligands for the targeting of oncogenic miRNA biogenesis based on the 2-deoxystreptamine scaffold. The latter is part of the aminoglycoside neomycin and is known to play an essential role in the RNA interaction of this class of RNA binders. 2-deoxystreptamine was thus conjugated to natural and artificial nucleobases to obtain new binders of the oncogenic miR-372 precursor (pre-miR-372). We identified some conjugates exhibiting a similar biological activity to previously synthesized neomycin analogs and studied their mode of binding with the target pre-miR-372.

New selective cyclooxygenase-2 inhibitors from cyclocoumarol: Synthesis, characterization, biological evaluation and molecular modeling.

In this work, a serie of cyclocoumarol derivatives was designed, synthesized, characterized and studied for their potentialities as selective inhibitors of COX-2. All target compounds have been screened for their anti-inflammatory activity by the assay of PGE2 production. Among them, compound 5d exhibited the most potent inhibitory activity with a PGE2 inhibition compared to NS-398 (79% and 88% respectively) and showed non-inhibitory activity towards the COX-1 enzyme. Docking studies revealed the capacity of this compound to occupy the selective COX-2 cavity establishing additional hydrogen bonds between the oxygen of the methoxy group and the His90 and Arg513 of the binding site of the enzyme.

Update on COX-2 Selective Inhibitors: Chemical Classification, Side Effects and their Use in Cancers and Neuronal Diseases.

Inflammation is a complex phenomenon necessary in human defense mechanisms but also involved in the development of some human diseases. The discovery of cyclooxygenase-2 (COX- 2) improved the pharmacology of nonsteroidal anti-inflammatory drugs (NSAID) giving a clear mechanism for prostaglandin regulation in vivo and providing a new target for the development of COX-2-selective drugs without gastrointestinal side-effects. Keeping in view the importance of this pharmacological class, several literature reports have underlined the impact of these antiinflammatory compounds in therapeutics. The present review considers the most recently published literature concerning COX-2 inhibitors until 2016. Through a wide chemical classification, the last developments concerning this therapeutic family by highlighting structure-activity relationships insights and mechanisms are presented. A summary of the principal adverse effects observed and an overview of the new potential therapeutic indications for COX-2 inhibitors are also reported.

An efficient and selective microwave-assisted Claisen-Schmidt reaction for the synthesis of functionalized benzalacetones.

A simple and direct method for the Claisen-Schmidt reaction to prepare functionalized α,ß-unsaturated ketones has been developed. Microwave irradiation of aldehydes with acetone produces benzalacetones selectively without self-condensation product in very short reaction times and good yields. Graphical AbstractGraphics for use in the Table of Contents.