Trovafloxacin-DataSheet-生命科學(xué)試劑-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemETrovafloxacinCat.No.:HY-A0170CASNo.:147059-72-1分?式:C??H??F?N?O?分?量:416.35作?靶點(diǎn):Bacterial;Topoisomerase;Antibiotic作?通路:Anti-infection;CellCycle/DNADamage儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1monthBIOLOGICALACTIVITY?物活性Trovafloxacin?種?譜喹諾酮類抗?素，對?蘭?陽性，?蘭?性和厭氧具有有效的活性。Trovafloxacin可阻斷DNA促旋酶(DNAgyrase)和拓?fù)洚悩?gòu)酶IV(topoisomeraseIV)的活性。Trovafloxacin也?種有效的，選擇性的，?服活性的Pannexin1通道(PANX1)抑制劑，對PANX1內(nèi)向電流的IC50為4μM。Trovafloxacin不抑制connexin43gapjunction或PANX2。Trovafloxacin通過抑制PANX1導(dǎo)致凋亡細(xì)胞碎?失調(diào)。IC50&TargetIC50:4μM(Pannexin1channel(PANX1))[2]Gram-positive,Gram-negativeandanaerobicorganisms[3]DNAgyrase[3]TopoisomeraseIV[3]體外研究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?邊的抑制劑?師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.體內(nèi)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?邊的抑制劑?師www.MedChemECaution:Producthas