grant
Unraveling the spectrum of intrabacterial amide hydrolysis to develop new classes of pyrazinoic acid prodrugs against pyrazinamide resistant Mycobacterium tuberculosis
Organization RUTGERS BIOMEDICAL AND HEALTH SCIENCESLocation Newark, UNITED STATESPosted 2 Jun 2025Deadline 31 May 2030
NIHUS FederalResearch GrantFY2025AcidsAmidesAminesAntitubercular DrugsAssayBacteriaBioassayBiological AssayBlood PlasmaCause of DeathCell BodyCell WallCellsCytoplasmCytosolDNA mutationDataDevelopmentDiffuseDiffusionDrug KineticsDrug PrecursorsDrug resistanceDrug resistance in MtbDrug resistance in Mycobacterium TuberculosisDrug resistant M TuberculosisDrug resistant MtbDrug resistant Mycobacteria TuberculosisDrug usageDrugsEnzyme GeneEnzymesFrequenciesFutureGenerationsGenesGenetic ChangeGenetic defectGenetic mutationHydrolysisHydrophobicityINH resistanceINH resistantIn VitroInfectious AgentIntermediary MetabolismIsoniazid resistanceIsoniazid resistantIsonicotinic Acid HydrazideKnowledgeLibrariesLinkLipidsLiver MicrosomesM . tuberculosis resistanceM tbM tuberculosisM tuberculosis infectionM. tbM. tb infectionM. tuberculosisM. tuberculosis infectionM.tb infectionM.tuberculosis infectionMTB infectionMeasuresMedicationMedicinal ChemistryMetabolic ProcessesMetabolismMethodsMiceMice MammalsModernizationMtb drug resistanceMtb resistanceMurineMusMutationMycobacterium tuberculosisMycobacterium tuberculosis (MTB) infectionMycobacterium tuberculosis infectionMycobacterium tuberculosis resistancePZA resistancePZA resistantPenetrationPersonsPharmaceutic ChemistryPharmaceutical ChemistryPharmaceutical PreparationsPharmacokineticsPlasmaPlasma SerumPopulationPredispositionPro-DrugsProdrugsProteinsPublic HealthPyrazinamidePyrazinamide resistancePyrazinamide resistantPyrazinecarboxamideRelapseResistanceResistance to PZAResistance to PyrazinamideResistant to PZAResistant to PyrazinamideReticuloendothelial System, Serum, PlasmaRifampicin resistanceRifampicin resistantRifampin resistanceRifampin resistantRiskRoleStructureStructure-Activity RelationshipSubstrate SpecificitySusceptibilityTB drugsTB infectionTB therapyTB treatmentTestingToxic effectToxicitiesTreatment ProtocolsTreatment RegimenTreatment ScheduleTuberculosisWorkacylamidaseacylaseamidaseamineanaloganti-TB drugsanti-tuberculosis drugscell envelopechemical librarychemical structure functiondesigndesigningdevelopmentaldiffuseddiffusesdiffusingdiffusionsdisseminated TBdisseminated tuberculosisdrug developmentdrug metabolismdrug resistance M Tuberculosisdrug resistance Mycobacteria Tuberculosisdrug resistantdrug resistant M.tbdrug usedrug/agentgenome mutationglobal healthhydrophilicityimprovedin vivoinfection due to Mycobacterium tuberculosisinfectious organismisoniazidlead optimizationmachine learning based modelmachine learning based prediction modelmachine learning based predictive modelmachine learning modelmachine learning predictionmachine learning prediction modelmouse modelmtbmurine modelnew approachesnovelnovel approachesnovel strategiesnovel strategypandemicpandemic diseasepreventpreventingpyrazine-2-carboxylic acidpyrazinecarboxylic acidpyrazinoic acidrational designresistance in M . tuberculosisresistance in Mycobacterium tuberculosisresistance mechanismresistance strainresistance to Drugresistance to isoniazidresistance to rifampicinresistance to rifampinresistantresistant M . tuberculosisresistant Mtbresistant Mycobacterium tuberculosisresistant mechanismresistant strainresistant to Drugresistant to isoniazidresistant to rifampicinresistant to rifampinsmall moleculesmall molecule librariessocial rolestructure function relationshipsuccesstooltreat M. tuberculosistreat Mtbtreat Mycobacterium tuberculosistreat tbtreat tuberculosistuberculosis drugstuberculosis infectiontuberculosis therapytuberculosis treatmenttuberculous spondyloarthropathy
Description preview
ABSTRACT
Mycobacterium tuberculosis (Mtb) infection is a global health pandemic claiming 1.5 million lives each
year. Current tuberculosis (TB) therapies are challenged by drug resistance, characterized by mutations that
render approved drugs increasingly less effective. PZA is a critical component of first-line TB therapy. It allows
for shorter…
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