Search results for " sensitivity"

showing 10 items of 947 documents

A peptide from human β thymosin as a platform for the development of new anti-biofilm agents for Staphylococcus spp. and Pseudomonas aeruginosa

2016

Conventional antibiotics might fail in the treatment of biofilm-associated infections causing infection recurrence and chronicity. The search for antimicrobial peptides has been performed with the aim to discover novel anti-infective agents active on pathogens in both planktonic and biofilm associated forms. The fragment 9-19 of human thymosin β4 was studied through 1 μs MD simulation. Two main conformations of the peptide were detected, both constituted by a central hydrophobic core and by the presence of peripheral charged residues suggesting a possible mechanism of interaction with two models of biological membranes, related to eukaryotic or bacterial membrane respectively. In addition, …

Models Molecular0301 basic medicineStaphylococcus aureusPhysiology030106 microbiologyAntimicrobial peptidesSettore BIO/05 - ZoologiaPeptideMicrobial Sensitivity TestsMolecular Dynamics SimulationBiologymedicine.disease_causeSettore BIO/19 - Microbiologia GeneraleApplied Microbiology and BiotechnologyMicrobiologyStructure-Activity Relationship03 medical and health sciencesAnti-Infective AgentsmedicineHumansAmino Acid SequencePeptide sequencechemistry.chemical_classificationPseudomonas aeruginosaAntimicrobial peptides Molecular dynamics Staphylococcal biofilms ThymosinBiofilmThymosinGeneral MedicineAntimicrobialSettore CHIM/08 - Chimica FarmaceuticaThymosin030104 developmental biologychemistryBiochemistrySettore CHIM/03 - Chimica Generale E InorganicaBiofilmsPseudomonas aeruginosaPeptidesAntibacterial activityBiotechnology
researchProduct

Synthesis, physicochemical characterization, cytotoxicity, antimicrobial, anti-inflammatory and psychotropic activity of new N-[1,3-(benzo)thiazol-2-…

2012

Abstract A series of new N-[(benzo)thiazol-2-yl]-2/3-[3,4-dihydroisoquinolin-2(1H)-yl]ethan/propanamide derivatives was synthesized and characterized by 1H, 13C NMR and IR spectroscopy and mass-spectrometry. A single crystal X-ray study of N-(1,3-benzothiazol-2-yl)-2-[3,4-dihydroisoquinolin-2(1H)-yl]ethanamide is reported to determine its conformational feature. The investigated compounds were found to be active in psychotropic in vivo, anti-inflammatory in vivo and cytotoxicity in vitro screening. They possess marked sedative action, reveal high anti-inflammatory activity, have selective cytotoxic effects and NO-induction ability concerning tumour cell lines. Some of the compounds synthesi…

Models MolecularAntifungal AgentsStereochemistrymedicine.drug_classInfrared spectroscopyAntineoplastic AgentsMicrobial Sensitivity TestsCarrageenanCrystallography X-RayAnti-inflammatorychemistry.chemical_compoundMiceStructure-Activity RelationshipSeizuresCell Line TumorDrug DiscoverymedicineAnimalsEdemaHumansBenzothiazolesThiazoleCytotoxicityHypoxiaPsychomotor AgitationCell ProliferationPharmacologyPsychotropic DrugsBacteriaDose-Response Relationship DrugMolecular StructureTetrahydroisoquinolineChemistry PhysicalOrganic ChemistryAnti-Inflammatory Agents Non-SteroidalFungiGeneral MedicineCarbon-13 NMRAntimicrobialIsoquinolinesPropanamideAnti-Bacterial AgentschemistryNIH 3T3 CellsDrug Screening Assays AntitumorAnesthesia InhalationEuropean journal of medicinal chemistry
researchProduct

An Experimental Toolbox for Structure‐Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics

2021

Abstract FabF (3‐oxoacyl‐[acyl‐carrier‐protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target for new antibiotics. Here, we focus on FabF from P. aeruginosa (PaFabF) as antibiotics against this pathogen are urgently needed. To facilitate exploration of this target we have set up an experimental toolbox consisting of binding assays using bio‐layer interferometry (BLI) as well as saturation transfer difference (STD) and WaterLOGSY NMR in addition to robust conditions for structure determination. The suitability of the toolbox to support structure‐based design of FabF inhibitors was demonstrated through the …

Models MolecularBio-layer interferometrymedicine.drug_classAntibioticsMicrobial Sensitivity TestsCrystallography X-RayLigandsBiochemistryantibiotics3-Oxoacyl-(Acyl-Carrier-Protein) SynthaseDrug Discoverymedicinebio-layer interferometryGeneral Pharmacology Toxicology and PharmaceuticsEnzyme InhibitorsPharmacologyligand-based NMRVirtual screeningBiological ProductsFull PaperMolecular StructureChemistryOrganic ChemistryLimitingFull Papersvirtual screeningCombinatorial chemistrystructure-based designAnti-Bacterial AgentsSaturation transferPseudomonas aeruginosaMolecular MedicineStructure basedChemmedchem
researchProduct

Computational Identification of Chemical Compounds with Potential Activity against Leishmania amazonensis using Nonlinear Machine Learning Techniques.

2019

Leishmaniasis is a poverty-related disease endemic in 98 countries worldwide, with morbidity and mortality increasing daily. All currently used first-line and second-line drugs for the treatment of leishmaniasis exhibit several drawbacks including toxicity, high costs and route of administration. Consequently, the development of new treatments for leishmaniasis is a priority in the field of neglected tropical diseases. The aim of this work is to develop computational models those allow the identification of new chemical compounds with potential anti-leishmanial activity. A data set of 116 organic chemicals, assayed against promastigotes of Leishmania amazonensis, is used to develop the the…

Models MolecularChemical compoundComputer scienceAntiprotozoal AgentsDrug Evaluation PreclinicalMachine learningcomputer.software_genre01 natural sciencesMachine Learningchemistry.chemical_compoundParasitic Sensitivity TestsMolecular descriptorDrug DiscoveryLeishmaniaComputational modelLeishmania amazonensisVirtual screeningbiologyArtificial neural networkbusiness.industryGeneral Medicinebiology.organism_classification0104 chemical sciencesSupport vector machine010404 medicinal & biomolecular chemistryIdentification (information)chemistryArtificial intelligencebusinesscomputerSoftwareCurrent topics in medicinal chemistry
researchProduct

Cinoxacin complexes with divalent metal ions. Spectroscopic characterization. Crystal structure of a new dinuclear Cd(II) complex having two chelate-…

1998

Several cinoxacin (HCx) complexes with divalent metal ions have been prepared and characterized by spectroscopic techniques. The crystal structure of [Cd 2 (Cx) 4 (H 2 O) 2 ] · 10H 2 O has been determined by X-ray diffraction. The complex is triclinic, space group with unit-cell dimensions: a =10.412(2), b =11.119(2), c =13.143(6)A, α=76.78(4)°, β =74.59(3)°, γ =77.12(3)°, V =1406.0(8) A 3 . In this complex each cadmium atom is heptacoordinated; the metal environment is formed by two O keto and two O carbox atoms from two different cinoxacinate monoanions, two carboxylate oxygen atoms from a third cinoxacinate ligand and by one water oxygen atom on the seventh position. Two of the cinoxacin…

Models MolecularDenticityStereochemistryCinoxacinCarboxylic AcidsCrystal structureMicrobial Sensitivity TestsTriclinic crystal systemCrystallography X-RayBiochemistryInorganic ChemistryMetalchemistry.chemical_compoundStructure-Activity RelationshipAnti-Infective AgentsmedicineEscherichia coliOrganometallic CompoundsChelationCarboxylateChelating Agents4-QuinolonesLigandCrystallographychemistryvisual_artvisual_art.visual_art_mediumCinoxacinmedicine.drugCadmiumJournal of inorganic biochemistry
researchProduct

Synthesis, biological evaluation and chemometric analysis of indazole derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of antichag…

2012

Chagas disease chemotherapy, currently based on only two drugs, nifurtimox and benznidazole, is far from satisfactory and therefore the development of new antichagasic compounds remains an important goal. On the basis of antichagasic properties previously described for some 1,2-disubstituted 5-nitroindazolin-3- ones (21, 33) and in order to initiate the optimization of activity of this kind of compounds, we have prepared a series of related analogs (22-32, 34-38, 58 and 59) and tested in vitro these products against epimastigote forms of Trypanosoma cruzi. 2-Benzyl-1-propyl (22), 2-benzyl-1-isopropyl (23) and 2-benzyl-1-butyl (24) derivatives have shown high trypanocidal activity and low un…

Models MolecularDrugChagas diseaseIndazolesStereochemistryTrypanosoma cruzimedia_common.quotation_subjectStructure-Activity Relationshipchemistry.chemical_compoundParasitic Sensitivity TestsDrug DiscoverymedicineNifurtimoxTrypanosoma cruziBiological evaluationmedia_commonPharmacologyIndazoleDose-Response Relationship DrugMolecular StructurebiologyOrganic ChemistryGeneral Medicinemedicine.diseasebiology.organism_classificationTrypanocidal AgentsCombinatorial chemistrychemistryBenznidazolemedicine.drugEuropean Journal of Medicinal Chemistry
researchProduct

Targeting the Class A Carbapenemase GES-5 via Virtual Screening

2020

The worldwide spread of &beta

Models MolecularDrugantibiotic resistanceGES-5Antibiotic resistancemedia_common.quotation_subjectIn silicoDrug Evaluation Preclinicallcsh:QR1-502Guyana extended-spectrum-β-lactamaseMicrobial Sensitivity TestsComputational biologyBiologyBiochemistrybeta-LactamasesArticlelcsh:Microbiologyguyana extended-spectrum-β-lactamasecarbapenemase03 medical and health sciencesAntibiotic resistanceBacterial ProteinsDrug Resistance BacterialHumansAntibiotic resistance; GES-5; Guyana extended-spectrum-β-lactamase; carbapenemase; virtual screening; docking; noncovalent inhibitionges-5noncovalent inhibitionMolecular Biology030304 developmental biologymedia_common0303 health sciencesVirtual screening030306 microbiologyAntibiotic resistance; Carbapenemase; Docking; GES-5; Guyana extended-spectrum-β-lactamase; Noncovalent inhibition; Virtual screeningHit to leadvirtual screeningAntimicrobialAnti-Bacterial AgentsCarbapenemsdockingBiomolecules
researchProduct

Optimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal…

2013

The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 subs…

Models MolecularImidazopyridineMolecular modelNitrilePyridinesStereochemistryCathepsin LTrypanosoma brucei bruceiSubstituentCysteine Proteinase InhibitorsCrystallography X-RayLigandsBiochemistryStructure-Activity Relationshipchemistry.chemical_compoundParasitic Sensitivity TestsNitrilesDrug DiscoveryHumansMoietyGeneral Pharmacology Toxicology and PharmaceuticsTriazinePharmacologyDose-Response Relationship DrugMolecular StructurebiologyTriazinesChemistryLigandOrganic ChemistryImidazolesActive siteCysteine Endopeptidasesbiology.proteinMolecular MedicineChemMedChem
researchProduct

Antimicrobial Peptides and Their Superior Fluorinated Analogues: Structure-Activity Relationships as Revealed by NMR Spectroscopy and MD Calculations

2010

9 pag., 6 fig, 3 tab.

Models MolecularMagnetic Resonance SpectroscopyHalogenationProtein ConformationDiffusionAntimicrobial peptidesMicrobial Sensitivity TestsMolecular Dynamics SimulationBiochemistryMicelleStructure-Activity RelationshipMolecular dynamicsantimicrobial peptidesNMR spectroscopyComputational chemistryfluorineEscherichia coliOrganic chemistryAmino Acid SequenceMolecular BiologyAqueous solutionMolecular StructureChemistryOrganic ChemistrySodium Dodecyl SulfateWaterNuclear magnetic resonance spectroscopyAntimicrobialmolecular dynamicsSolutionsMembranemembranespeptidesMolecular MedicineAntimicrobialSDS micellesOligopeptidesAntimicrobial Cationic Peptides
researchProduct

(Trifluoromethoxy)Phenylboronic Acids: Structures, Properties, and Antibacterial Activity.

2021

Three isomers of (trifluoromethoxy)phenylboronic acids were studied in the context of their physicochemical, structural, antimicrobial and spectroscopic properties. They were characterized by 1H, 13C, 11B and 19F NMR spectroscopy. The acidity of all the isomers was evaluated by both spectrophotometric and potentiometric titrations. The introduction of the -OCF3 group influences the acidity, depending, however, on the position of a substituent, with the ortho isomer being the least acidic. Molecular and crystal structures of ortho and para isomers were determined by the single crystal XRD method. Hydrogen bonded dimers are the basic structural motives of the investigated molecules in the sol…

Models MolecularMagnetic Resonance SpectroscopyPotentiometric titrationSubstituentMolecular ConformationPharmaceutical ScienceContext (language use)Crystal structureMicrobial Sensitivity TestsDFTMedicinal chemistryArticleOCF<sub>3</sub>Analytical Chemistrylcsh:QD241-441chemistry.chemical_compoundlcsh:Organic chemistryDrug StabilityIsomerismtrifluoromethoxyDrug DiscoveryMoleculePhysical and Theoretical ChemistryMolecular StructureHydrogen bondOrganic ChemistryBoronic AcidsNMRAnti-Bacterial AgentsantibacterialchemistryChemistry (miscellaneous)Intramolecular forceX-RayMolecular MedicineisomersOCF3Derivative (chemistry)Molecules (Basel, Switzerland)
researchProduct