Search results for "triketones"

showing 2 items of 2 documents

Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE

2018

Abstract: In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8CTE, fused benzo[b]thiophenes and ,'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate-to-excellent activity (12%-90% inhibition of the target enzyme at 20m). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-to…

Cell SurvivalLeishmania mexicanaProtozoan ProteinsADME-Tox; Benzo[b]thiophenes; Cysteine protease; Leishmaniasis; TriketonesThiophenesCysteine Proteinase Inhibitors010402 general chemistry01 natural sciencesBiochemistryLeishmania mexicanaCysteine Proteinase InhibitorsCell LineInhibitory Concentration 50Structure-Activity RelationshipCysteine ProteasesCatalytic DomainDrug DiscoveryHumansStructure–activity relationshipcysteine proteaseBinding siteADME-Tox; benzo[b]thiophenes; cysteine protease; leishmaniasis; triketones; Biochemistry; Molecular MedicineBiologyleishmaniasisPharmacologychemistry.chemical_classificationVirtual screeningBinding Sitesbiology010405 organic chemistryPharmacology. TherapyOrganic Chemistrytriketonesbiology.organism_classificationCysteine protease0104 chemical sciencesMolecular Docking SimulationChemistryEnzymeBiochemistrychemistryDocking (molecular)ADME-ToxMolecular Medicinebenzo[b]thiophenes
researchProduct

DIAGSOL : development of a new functional marker of exposure to herbicides B-triketones in an agricultural soil

2020

Numerous herbicides target an enzyme found not only in weeds but also in « non-target organisms » such as microorganisms. This proof-of-concept study aims to use microbial gene encoding the targeted enzyme or the targeted enzyme itself as a marker for herbicide exposure in soils. The hppd gene and the encoded enzyme (HPPD; 4-hydroxyphenylpyruvate dioxygenase), targeted by B-triketone herbicides, are the subject of this study. In silico analyses reveal that the hppd gene is spread out in all bacterial phyla. Primers specific to this gene were designed. This primer pair is used to measure the abundance, the composition and the diversity of the hppd bacterial community in soil microcosms expos…

[SDV.SA]Life Sciences [q-bio]/Agricultural sciences[SDV.EE]Life Sciences [q-bio]/Ecology environment[SDV.SA] Life Sciences [q-bio]/Agricultural sciencesCommunautés microbiennesMicroorganismsMicrobial communitiesBiomarkerEnzyme HPPDOrganismes non-ciblesHPPD enzymeHerbicides β-Tricétones[SDV.EE] Life Sciences [q-bio]/Ecology environment[SDV.EE.ECO]Life Sciences [q-bio]/Ecology environment/EcosystemsBioessaiBiomarqueurNon-target organisms[SDV.EE.ECO] Life Sciences [q-bio]/Ecology environment/EcosystemsMicrobial hppd geneÉcotoxicologie microbienneBioassayMicroorganismeMicrobial ecotoxicologyΒ-Triketones herbicidesGène hppd microbien
researchProduct