2001
Novel Approaches to Polynuclear Platinum Pro-Drugs. Selective Release of Cytotoxic Platinum−Spermidine Species through Hydrolytic Cleavage of Carbamates
Hegmans A, Qu Y, Kelland L, Roberts J, Farrell N. Novel Approaches to Polynuclear Platinum Pro-Drugs. Selective Release of Cytotoxic Platinum−Spermidine Species through Hydrolytic Cleavage of Carbamates. Inorganic Chemistry 2001, 40: 6108-6114. PMID: 11703107, DOI: 10.1021/ic010509a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCarbamatesCatalysisChromatography, High Pressure LiquidFemaleHumansHydrogen-Ion ConcentrationHydrolysisInhibitory Concentration 50Leukemia L1210MiceMolecular StructureNuclear Magnetic Resonance, BiomolecularOrganoplatinum CompoundsOvarian NeoplasmsPolyaminesProdrugsSpermidineSpermineStereoisomerismStructure-Activity RelationshipTemperatureTumor Cells, CulturedConceptsDinuclear platinum compoundsPt–Cl bondsPreliminary biological assaysN-butyl side chainsMagnitude less cytotoxicPolynuclear platinumSecond generation analogsNMR spectroscopyPolyamine linkersQuaternary nitrogenFMOC derivativesConformational isomersDerivatives 4Electrostatic contributionSide chainsHydrolytic cleavageSpermidine moietyGreater selectivityOral deliveryTherapeutic indexPlatinum drugsRate constantsCellular uptakeN-propylBiological assays
1999
Comparison of cytotoxicity and cellular accumulation of polynuclear platinum complexes in L1210 murine leukemia cell lines
Roberts J, Peroutka J, Beggiolin G, Manzotti C, Piazzoni L, Farrell N. Comparison of cytotoxicity and cellular accumulation of polynuclear platinum complexes in L1210 murine leukemia cell lines. Journal Of Inorganic Biochemistry 1999, 77: 47-50. PMID: 10626353, DOI: 10.1016/s0162-0134(99)00137-3.Peer-Reviewed Original ResearchConceptsPolynuclear platinum complexesPlatinum complexesDiamine linkerL1210 cell lineDinuclear platinum complexesTrinuclear platinum complexL1210 murine leukemia cell lineL1210/DDPDinuclear complexesAnticancer profileChemical featuresCytotoxicity profileCellular uptakeBBR3464LinkerMurine leukemia cell lineComplexesTransCharge contributesClinical agentsCytotoxicityUptake pathwayCellular accumulationAntitumor activityPlatinum
1996
Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration
Bear H, McFadden A, Kostuchenko P, Lipshy K, Hamad G, Turner A, Roberts J, Carr M, Carr S, Grant S. Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration. Anti-Cancer Drugs 1996, 7: 299-306. PMID: 8792004, DOI: 10.1097/00001813-199605000-00010.Peer-Reviewed Original ResearchConceptsBryostatin 1Normal murine spleen cellsT-cell activation marker CD69PKC activityActivation marker CD69Single bolus injectionEarly lymphocyte activationSingle intravenous administrationAnti-tumor effectsNormal host tissuesCell surface phenotypeProtein kinase CMurine spleen cellsPlasma levels resultsRegulate protein kinase CAnti-cancer agentsControl miceMarked splenomegalyBolus injectionIntravenous administrationC57BI/6 miceSpleen cellsSplenocyte proliferationSplenic lymphocytesSurface phenotype
1992
Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action.
Farrell N, Kelland LR, Roberts JD, Van Beusichem M. Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and human tumor panels and studies on their mechanism of action. Cancer Research 1992, 52: 5065-72. PMID: 1516063.Peer-Reviewed Original ResearchConceptsPlatinum antitumor complexesPlanar ligandsPyridine complexesAmmine complexesAntitumor complexesNew trans platinum complexesCell linesHuman tumor cell linesTrans-platinum complexesTumor cell linesPreliminary mechanistic studiesMurine L1210Rate of reactionFormula transMechanism of actionTrans complexesTrans geometryImportant biomoleculesSteric hindranceThymus DNAHuman tumor panelOvarian carcinoma cell linesCarcinoma cell linesPotential new classDNA synthesis
1986
Regional fibrosis after intraperitoneal administration of mafosfamide
Roberts J, Newman R, Kimberly P, Hacker M. Regional fibrosis after intraperitoneal administration of mafosfamide. Investigational New Drugs 1986, 4: 61-65. PMID: 2939038, DOI: 10.1007/bf00172019.Peer-Reviewed Original Research
1984
Efficacy and toxicity of 4-(2-sulfonatoethylthio)-cyclophosphamide cyclohexylamine salt (ASTA Z 7557, INN mafosfamide) after intraperitoneal administration to mice
Roberts J, Hacker M, Newman R, McCormack J, Krakoff I. Efficacy and toxicity of 4-(2-sulfonatoethylthio)-cyclophosphamide cyclohexylamine salt (ASTA Z 7557, INN mafosfamide) after intraperitoneal administration to mice. Investigational New Drugs 1984, 2: 215-220. PMID: 6469517, DOI: 10.1007/bf00232354.Peer-Reviewed Original ResearchConceptsBladder toxicityIntraperitoneal administrationAcute bladder toxicityPhosphoramide mustardAZ therapyHepatic fibrosisIntravenous administrationLocal toxicityTherapeutic indexMurine systemAdministrationCyclophosphamide analoguesFurther studiesSpontaneous activationAssociated riskToxicityCyclohexylamine saltFibrosisTherapyMice