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 `R2 “ 0.713 ̆ and test set `Q2ext “ 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

Straightforward synthesis of PET tracer precursors used for the early diagnosis of Alzheimers disease through Suzuki–Miyaura cross-coupling reactions

International audienceIn positron emission tomog. [11C] PIB, Pittsburgh Compd.- B, is currently the most widely used radiopharmaceutical for the early diagnosis of Alzheimer's disease. Synthetic routes for the prepn. of the precursor of [11C] PIB are reported in the literature. These strategies require multiple steps and the use of protecting groups. This paper describes a simple 1- step synthesis of the precursor of [11C] PIB through a Suzuki- Miyaura coupling reaction using thermal conditions or microwave activation. These methods were successfully applied to the synthesis of various 2- arylbenzothiazole and 2- pyridinylbenzothiazole compds. including [18F] precursor derivs. of PIB contg. a nitro functio

Editorial: New Experimental and Computational Tools for Drug Discovery: From Chemistry to Biology. Part-1

Editoria

Coumarins derivatives and inflammation: Review of their effects on the inflammatory signaling pathways

International audienceNatural and synthetic coumarins have been extensively described in the literature as effective drugs with several pharmacological activities. Many valuable publications have shown the anti-inflammatory potential of these compounds suggesting that coumarins could be an interesting scaffold for developing new therapeutic anti-inflammatory agents. However, despite the continuous efforts of research in this field, no major breakthrough was yet achieved and only a few coumarin-like drugs are commercially available.In the present article, we reviewed the most relevant studies conducted in the last two decades (2000–2021) and presenting evidence for the anti-inflammatory mechanisms of coumarins. The review provides a comprehensive survey of scientific research revealing through multiple in vitro and in vivo models the effect of natural and synthetic coumarins on components of the Toll-like receptors (TLR), Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), Inflammasomes, mitogen-activated protein kinase (MAPK), nuclear factor- κ-light-chain-enhancer of activated B cells (NF- κB) and transforming growth factor-β/small mothers against decapentaplegic (TGF-β/SMAD) pathways

Conception, Synthesis, Characterization and Antimicrobial Evaluation of New Ferrocene-Based Derivatives Inspired by the Bisacodyl Lead Structure

Abstract: The antibacterial activity of bisacodyl, a drug used in therapeutic as laxative, and its ferrocenyl analogues was investigated against Gram-positive and Gram-negative foodborne pathogens including Listeria monocytogenes, Escherichia coli, Enterococcus faecalis, Salmonella enterica, Micrococcus luteus and Staphylococcus aureus. The results showed that most of these compounds exhibit an excellent antimicrobial activity, and the bisacodyl analogues seemed to be more bactericides than bacteriostatic

Diarylmethanes as potential anti colorectal cancer agents: Synthesis, In vitro and in silico studies

International audienc

Conception, synthesis, characterization and antimicrobial evaluation of new ferrocene-based derivatives inspired by the bisacodyl lead structure.

International audienc

Data of the quantification of the influence of DMSO concentration on the kinetic of interaction between TNFα and SPD304

International audienceThe data presented here are related to the article entitled “New contributions to the drug profile of TNFα inhibitor SPD304: affinity, selectivity ADMET considerations” published in the European Journal of pharmacology. As DMSO is usually used as a co-solvent to dissolve low aqueous soluble small molecules, such as SPD304, we have investigated the influence of its concentration on the kinetic of interaction between tumor necrosis factor α (TNF-α) and its inhibitor, SPD304. The presented data, acquired using a surface acoustic wave sensor, can be used in further biological studies to compare the kinetic of interaction between proteins/small molecules in general and TNFα/inhibitors in particular. The estimated dissociation constant can be compared to other ones to statute on the degree of affinity between a protein and a given molecule

Synthesis of N-protected β-3-amino nitriles: study of their hydrolysis involving a nitrilase-catalysed step.

International audienc

Plant flavonoids as modulators of the aryl hydrocarbon receptor

The aryl hydrocarbon receptor (AhR) is a transcription factor deeply implicated in health and diseases. Historically identified as a sensor of xenobiotics and mainly toxic substances, AhR has recently become an emerging pharmacological target in cancer, immunology, inflammatory conditions, and aging. Multiple AhR ligands are recognized, with plant occurring flavonoids being the largest group of natural ligands of AhR in the human diet. The biological implications of the modulatory effects of flavonoids on AhR could be highlighted from a toxicological and environmental concern and for the possible pharmacological applicability. Overall, the possible AhR-mediated harmful and/or beneficial effects of flavonoids need to be further investigated, since in many cases they are contradictory. Similar to other AhR modulators, flavonoids commonly exhibit tissue, organ, and species-specific activities on AhR. Such cellular-context dependency could be probably beneficial in their pharmacotherapeutic use. Flavones, flavonols, flavanones, and isoflavones are the main subclasses of flavonoids reported as AhR modulators. Some of the structural features of these groups of flavonoids that could be influencing their AhR effects are herein summarized. However, limited generalizations, as well as few outright structure-activity relationships can be suggested on the AhR agonism and/or antagonism caused by flavonoids.PROTECTED - PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communicatio