86 research outputs found
The PHENIX Experiment at RHIC
The physics emphases of the PHENIX collaboration and the design and current
status of the PHENIX detector are discussed. The plan of the collaboration for
making the most effective use of the available luminosity in the first years of
RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program
available at http://www.rhic.bnl.gov/phenix
SYNTHESIS, INTERCALATION INTO DNA AND ANTICANCER ACTIVITY OF SOME 4,6- DIALKOXY-10-METHYL-PYRIDO [3,2-g] QUINOLINES
Preclinical evaluation of amino acid prodrugs of novel antitumor 2-(4-amino-3-methylphenyl)benzothiazoles
Novel 2-(4-aminophenyl)benzothiazoles (e.g., compounds 1 and 2) possess highly selective, potent antitumor properties in vitro and in vivo. Elucidation of the mechanism of action of this structurally simple class of compounds has occurred in parallel with selection of a candidate clinical agent. Antitumor benzothiazoles induce and are biotransformed by cytochrome P 450 1A1 to putative active, as well as inactive metabolites. Metabolic inactivation of the molecule has been thwarted by isosteric replacement of hydrogen with fluorine atoms at positions around the benzothiazole nucleus. Amino acid conjugation to the exocyclic primary amine function of 2-(4-aminophenyl)benzothiazoles has been used to overcome limitations posed by drug lipophilicity. Water soluble, chemically stable prodrugs rapidly and quantitatively revert to their parent amine in mice, rats, and dogs in vivo. Plasma concentrations of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (2) regenerated from the lysylamide prodrug (2b), sufficient to elicit cytocidal activity against ZR-75–1 and T47D human mammary carcinoma cell lines persist >6 h. The growth of breast (MCF-7) and ovarian (IGROV-1) xenograft tumors is significantly retarded by 2b. Manageable toxic side effects are reported from preclinically efficacious doses of 2b. Cytochrome P 450 1A1 protein expression, selectively induced in sensitive carcinoma cells, was detected in MCF-7 and IGROV-1 tumors 24 h after treatment of mice with 2b (20 mg/kg). The lysyl amide prodrug of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole is potentially suitable for clinical evaluation
Reactivity towards DNA and protein, cellular uptake, cytotoxic activity of a mononuclear copper(II) complex of the thioflavin-T (ThT)-based derivative
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