The Experts below are selected from a list of 180804 Experts worldwide ranked by ideXlab platform
Henri Brunner - One of the best experts on this subject based on the ideXlab platform.
-
Synthese Und Antitumoraktivität Von Platin(II)‐Komplexen Mit Cholesterinderivaten
Bulletin des Sociétés Chimiques Belges, 2010Co-Authors: Henri Brunner, G. SperlAbstract:Low-density-lipoprotein-receptor binding moieties were introduced into Pt(II) complexes in order to facilitate the selective transport into cancer cells. Cholesterol esters of aminoacids and 2,3-diaminopropionic acid were attached to the PtCl2 fragment via their NH2 groups. Steroidal amine and diamine ligands were synthesized and transformed into the corresponding dichloroplatinum(II) complexes. A steroidal carboxylic acid was prepared and coupled with the Pt(NH3)2 fragment. The antitumor activity of the compounds was tested towards the lymphatic P 388 leukemia of the CD2F1 Mouse and towards the human mammary carcinoma cell line MDA-MB 231. The Pt(II) complexes gave a maximum growth inhibition of 54%.
-
Antitumoraktive Platin(II)-Komplexe mit substituierten 2-Aminomethylpyridin-Liganden
Archiv der Pharmazie, 2010Co-Authors: Henri Brunner, Georg Nerl, Erwin Von Angerer, Norbert KnebelAbstract:Durch Umsetzung von K2P1CI4 mit den 2-Aminomethylpyridinliganden 9, 14 und 22 sind die entspr. Dichloroplatin(II)-Komplexe 3-5 erhaltlich. Die Verbindungen 3 und 22 zeigen beachtliche Bindungsaffinitaten zum Estrogenrezeptor. Gegen den hormonunabhangigen Tumor P388 der CD2F1-Maus erwiesen sich die Platin(II)-Komplexe 4 und 5 als schwach wirksam, Komplex 3 ist unwirksam. An der hormonunabhangigen MDA-MB 231-Zelllinie ist mit den Verbindungen 3-5,9,14 und 22 keine signifikante Wirkung erkennbar. An der hormonabhangigen MCF-7-Zellinie zeigen die Verbindungen 3-5,9,14 geringe Antitumorwirkung, der Ligand 22 dagegen hemmt stark. Antitumor-active Platinum(II) Complexes with Substltuted 2-Amlnomethylpyridine Ligands Reaction of K2PtCl4 with the substituted 2-aminomethylpyridines 9,14, and 22 affords the corresponding dichloroplatinum(II) complexes 3-5. Compounds 3 and 22 show remarkable relative binding affinities for the estrogen receptor. Towards the hormone-independant P388-tumor of the CD2F1-Mouse the platinum(II) complexes 4 and 5 are weakly active, complex 3 is inactive. Towards the hormone-independant MDA-MB 231-cell line, compounds 3-5, 9,14, and 22 exhibit no significant antitumor activity. Towards the hormonedependant MCF-7 cell line, compounds 3-5, 9, 14 show weak antitumor activity, whereas compound 22 exhibits strong inhibition.
-
Synthesis and antitumor activity of water-soluble 2-benzyl-1,2-diaminobutane-α-oxycarboxylatoplatinum(II) complexes
Inorganica Chimica Acta, 1992Co-Authors: Henri Brunner, Friedrich Maiterth, Barbara TreittingerAbstract:Abstract Nine new water-soluble platinum(II) complexes were synthesized and characterized. Racemic (±)-2-benzyl-1,2- diaminobutane or the corresponding enantiomers (+)-2-benzyl-1,2-diaminobutane and (−)-2-benzyl-1,2-diaminobutane were used as nitrogen chelate ligands. The chloride leaving groups of the resulting N,N′-2-benzyl- 1,2-diaminobutanedichloroplatinum(II) complexes were replaced by the anions of four α-hydroxycarboxylic acids to increase the water solubility. As α-hydroxycarboxylic acids, lactic acid, glycolic acid, mandelic acid and α- hydroxyisobutyric acid were used. For N,N′-2-benzyl-1,2-diaminobutane-O,O′-lactatoplatinum(II), the different geometrical and optical isomers were separated. The antitumor activity of the platinum(II) complexes was examined in vitro towards the MDA-MB 231 breast cancer cell line and in vivo towards the P 388 leukemia of the CD2F1 Mouse. Contrary to the insoluble dichloro complexes, the α-oxycarboxylatoplatinum(II) complexes exhibited good water solubility associated with a high antitumor activity.
James A. Bond - One of the best experts on this subject based on the ideXlab platform.
-
Determination of mutagenicity in tissues of transgenic mice following exposure to 1,3-butadiene and N-ethyl-N-nitrosourea.
Toxicology and applied pharmacology, 1992Co-Authors: Leslie Recio, Siv M. Osterman-golkar, György A. Csanády, Max J. Turner, Brian Myhr, Owen R. Moss, James A. BondAbstract:Abstract 1,3-Butadiene (BD) is carcinogenic in the B6C3F1 Mouse in multiple organs, including lung and liver. We conducted a study to measure the frequency of BD mutations in Mouse tissues using a transgenic Mouse (Muta Mouse; MM). MM is a BALB c × DBA 2 (CD2F1) Mouse that has a bacteriophage λ shuttle vector with the target gene lacZ integrated into the Mouse genome. Mice were exposed by inhalation to 625 ppm BD (6 hr/day) for 5 days and the lacZ − mutant frequency (mf) was determined in lung, bone marrow, and liver. The lacZ − mf in lung increased twofold above air-exposed control animals, but the bone marrow and liver samples did not exhibit an increase above background. N -ethyl- N -nitrosourea (250 mg/kg ip) was mutagenic in all three tissues examined. Studies on the biotransformation of BD using MM liver microsomes showed that the ratio between the rates of BD bioactivation to BD monoepoxide (BMO) and hydrolysis of BMO by epoxide hydrolases was approximately 40% less than this ratio using B6C3F1 Mouse liver microsomes. Quantitation of adducts of BMO to N-terminal valine in hemoglobin (Hb) in the MM revealed an adduct level of 3.7 pmol/mg globin. Using this value, the predicted Hb adduct level in MM would be approximately one-half of that measured in the B6C3F1 Mouse following similar exposures. These results indicate that BD induces mutations in vivo in a known murine target tissue, but strain differences in the biotransformation of BD should be considered in comparing the susceptibility of transgenic Mouse strains to mutation.
Barbara Treittinger - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis and antitumor activity of water-soluble 2-benzyl-1,2-diaminobutane-α-oxycarboxylatoplatinum(II) complexes
Inorganica Chimica Acta, 1992Co-Authors: Henri Brunner, Friedrich Maiterth, Barbara TreittingerAbstract:Abstract Nine new water-soluble platinum(II) complexes were synthesized and characterized. Racemic (±)-2-benzyl-1,2- diaminobutane or the corresponding enantiomers (+)-2-benzyl-1,2-diaminobutane and (−)-2-benzyl-1,2-diaminobutane were used as nitrogen chelate ligands. The chloride leaving groups of the resulting N,N′-2-benzyl- 1,2-diaminobutanedichloroplatinum(II) complexes were replaced by the anions of four α-hydroxycarboxylic acids to increase the water solubility. As α-hydroxycarboxylic acids, lactic acid, glycolic acid, mandelic acid and α- hydroxyisobutyric acid were used. For N,N′-2-benzyl-1,2-diaminobutane-O,O′-lactatoplatinum(II), the different geometrical and optical isomers were separated. The antitumor activity of the platinum(II) complexes was examined in vitro towards the MDA-MB 231 breast cancer cell line and in vivo towards the P 388 leukemia of the CD2F1 Mouse. Contrary to the insoluble dichloro complexes, the α-oxycarboxylatoplatinum(II) complexes exhibited good water solubility associated with a high antitumor activity.
Elise C. Kohn - One of the best experts on this subject based on the ideXlab platform.
-
In vitro and in vivo myelotoxicity of CAI to human and murine hematopoietic progenitor cells.
American journal of hematology, 1995Co-Authors: Donna A. Volpe, Kristina A. Cole, Mary Ann Sandeen, Elise C. KohnAbstract:Carboxyamido-triazole (CAI), an agent that targets calcium-sensitive signal transduction pathways, has both antiproliferative and antimetastatic properties. The objective of this study was to evaluate the myelotoxicity of CAI to normal human and murine hematopoietic cells. In vitro toxicity of CAI was determined by inhibition of myeloid [colony-forming unit-granulocyte/macrophage (CFU-gm)] and erythroid [burst-forming unit-erythroid (BFU-e)] colony formation in clonal assays. The effects of oral CAI on CD2F1 Mouse marrow and splenic cellularity, marrow progenitor content, and peripheral blood cell counts were assessed in relation to plasma CAI levels. In vitro, CAI caused a concentration-dependent inhibition of CFU-gm and BFU-e colonies following continuous drug exposure. Murine CFU-gm and BFU-e were inhibited > 90% by 10 and 15 micrograms/mL CAI, respectively. However, suppression of human CFU-gm and BFU-e did not exceed 65% at the same concentrations. In vivo, CAI reduced the number of CFU-gm and BFU-e per femur after the initial dose and through day 4. Variations in colony inhibition paralleled changes in CAI plasma concentrations. While colony inhibition increased in vitro with escalating drug concentrations, this was not observed in vivo with additional CAI doses. The low toxicity of CAI in vivo combined with the significant difference between toxicity for human and Mouse progenitors in vitro suggests a relatively low adverse potential to the bone marrow for this new signal transduction inhibitory agent.
Leslie Recio - One of the best experts on this subject based on the ideXlab platform.
-
Determination of mutagenicity in tissues of transgenic mice following exposure to 1,3-butadiene and N-ethyl-N-nitrosourea.
Toxicology and applied pharmacology, 1992Co-Authors: Leslie Recio, Siv M. Osterman-golkar, György A. Csanády, Max J. Turner, Brian Myhr, Owen R. Moss, James A. BondAbstract:Abstract 1,3-Butadiene (BD) is carcinogenic in the B6C3F1 Mouse in multiple organs, including lung and liver. We conducted a study to measure the frequency of BD mutations in Mouse tissues using a transgenic Mouse (Muta Mouse; MM). MM is a BALB c × DBA 2 (CD2F1) Mouse that has a bacteriophage λ shuttle vector with the target gene lacZ integrated into the Mouse genome. Mice were exposed by inhalation to 625 ppm BD (6 hr/day) for 5 days and the lacZ − mutant frequency (mf) was determined in lung, bone marrow, and liver. The lacZ − mf in lung increased twofold above air-exposed control animals, but the bone marrow and liver samples did not exhibit an increase above background. N -ethyl- N -nitrosourea (250 mg/kg ip) was mutagenic in all three tissues examined. Studies on the biotransformation of BD using MM liver microsomes showed that the ratio between the rates of BD bioactivation to BD monoepoxide (BMO) and hydrolysis of BMO by epoxide hydrolases was approximately 40% less than this ratio using B6C3F1 Mouse liver microsomes. Quantitation of adducts of BMO to N-terminal valine in hemoglobin (Hb) in the MM revealed an adduct level of 3.7 pmol/mg globin. Using this value, the predicted Hb adduct level in MM would be approximately one-half of that measured in the B6C3F1 Mouse following similar exposures. These results indicate that BD induces mutations in vivo in a known murine target tissue, but strain differences in the biotransformation of BD should be considered in comparing the susceptibility of transgenic Mouse strains to mutation.