Trovafloxacin-DataSheet-生命科学试剂-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemETrovafloxacinCat.No.:HY-A0170CASNo.:147059-72-1分⼦式:C₂₀H₁₅F₃N₄O₃分⼦量:416.35作⽤靶点:Bacterial;Topoisomerase;Antibiotic作⽤通路:Anti-infection;CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1monthBIOLOGICALACTIVITY⽣物活性Trovafloxacin⼀种⼴谱喹诺酮类抗⽣素，对⾰兰⽒阳性，⾰兰⽒性和厌氧具有有效的活性。Trovafloxacin可阻断DNA促旋酶(DNAgyrase)和拓扑异构酶IV(topoisomeraseIV)的活性。Trovafloxacin也⼀种有效的，选择性的，⼝服活性的Pannexin1通道(PANX1)抑制剂，对PANX1内向电流的IC50为4μM。Trovafloxacin不抑制connexin43gapjunction或PANX2。Trovafloxacin通过抑制PANX1导致凋亡细胞碎⽚失调。IC50&TargetIC50:4μM(Pannexin1channel(PANX1))[2]Gram-positive,Gram-negativeandanaerobicorganisms[3]DNAgyrase[3]TopoisomeraseIV[3]体外研究Trovafloxacin(20µM;24hours;HepG2cells)andtumornecrosisfactor(TNF;4ng/mL)incubationinducesapoptosisandincreasesleakageoflactatedehydrogenase(LDH)inHepG2cells[1].Trovafloxacin(20µM;24hours;HepG2cells)andTNF(4ng/mL)incubationincreasesexpressionofearlyNF-κB-relatedfactorsA20andIκBα[1].TrovafloxacinprolongsTNF-inducedactivationofMAPKsandIKKα/βactivationinHepG2[1].TrovafloxacinisapotentinhibitorofTO-PRO-3uptakebyapoptoticcells.TrovafloxacinalsoinhibitsATPreleasefromapoptoticcells.Trovafloxacindoesnotinhibitcaspase3/7activation,orcaspase-mediatedPANX1cleavageduringapoptosis[2].Trovafloxacinisequallyactiveagainstbothpenicillin-susceptibleand-resistantpneumococci,withMICsof1/2MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemE0.06-0.25mg/mLreportedformorethan700isolates.TheMICsofTrovafloxacinatwhich90%ofisolatesareinhibitedfor55isolatesofpneumococciis0.125μg/mL[3].ApoptosisAnalysis[1]CellLine:HepG2cellsConcentration:20µMIncubationTime:24hoursResult:ShowedagradualincreaseofAnnexinV-stainingandanincreasedleakageoflactatedehydrogenase(LDH)at24h.RT-PCR[1]CellLine:HepG2cellsConcentration:20µMIncubationTime:24hoursResult:CausedahigherincreaseinthetranscriptionofA20andIκBαinHepG2cells.体内研究Trovafloxacin(150mg/kg;oraladministration;maleC57BL/6Jmice)treatmentdisruptsTNF-inducedp65nucleartranslocation.TrovafloxacintreatmentincreasesexpressionofearlyNF-κB-relatedfactorsA20andIκBα[1].Trovafloxacin,whenadministeredincombinationwithlipopolysaccharide(LPS)orTNFtomiceinducesseverelivertoxicityassociatedwithvastapoptoticareasintheliver,increasedserumlevelsofalanineaminotransferases(ALT)andpro-inflammatorycytokines[1].AnimalModel:MaleC57BL/6Jmice(9-11-week-old)injectedwithrecombinantmurineTNFion[1]Dosage:150mg/kgAdministration:OraladministrationResult:Showedagreaternumberofcellswithincreasednuclear/cytoplasmicp65ratioinliver.REFERENCES[1].GiustariniG,etal.ThehepatotoxicfluoroquinolonetrovafloxacindisturbsTNF-andLPS-inducedp65nucleartranslocationinvivoandinvitro.ToxicolApplPharmacol.2020Mar15;391:114915.[2].PoonIK,etal.Unexpectedlinkbetweenanantibiotic,pannexinchannelsandapoptosis.Nature.2014Mar20;507(7492):329-34.[3].GootzTD,etal.Activityofthenewfluoroquinolonetrovafloxacin(CP-99,219)againstDNAgyraseandtopoisomeraseIVmutantsofStreptococcuspneumoniaeselectedinvitro.AntimicrobAgentsChemother.1996Dec;40(12):2691-7.McePdfHeight2/2MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthas