Naphthalamide a drug, amonafide, a DNA intercalator and an inhibitor of topoisomerase II m Resembled is conducted clinical trials for the treatment of tumor diseases. AMN showed a good activity T against fgfr signaling advanced breast cancer and as second therapy for AML, however, the amine 5-position of NMA in humans acetylated by N-acetyl transferase 2, the conversion of parent molecule into a toxic metabolite 5 amino acetyl acids. Polymorphisms in the NAT2 gene variant NAT2 enzyme activity due to the t between individuals requires as the Ph notypisierung the acetylation state or NAT2 genotyping in the different abbreviations: AMN, amonafide, A, 6 amino acids numonafide average 6 methoxyethylamino numonafide For the author: SuiHuang, Northwestern University Medical School, 303E Chicago Ave, Ward 11 240, Chicago, IL 60611th E mail: s huang2northwestern or Zhi Chen, State Key Laboratory of Infectious Diseases Diagnosis and Treatment, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
E mail: 1The authors Danusertib thank chenzhizju.cn partial funding from the Robert H. Lurie Comprehensive Cancer Center grant to SH from the National Institutes of Health. The two authors contributed equally S to this work. Re 16th U December 2010, 7th edition February 2011, accepted 8th 2011 Copyright 2011 © Neoplasia Press, Inc. All rights reserved 1522 8002/11 / $ 25.00 DOI 10.1593/neo.101738 Volume 13 Number neoplasia fifth com May 2011 pp 453 460 453 of AMN patients before treatment, a process that is composed expensive and initiation of treatment dir siege.
We have been the synthesis of amino derivatives of position 6 of the NMA called numonafides described. The numonafide with a free amine in position 6 and the other with a substituted amine in position 6 is not acetylated, w While the parental connection acetylated, AMN, that is largely determined by a biochemical test NAT2. Our previous characterization of numonafides shown that six amino numonafide methoxyethylaminonumonafide and 6, the best anti-tumor properties were in vitro. In this report, we characterized the mechanisms by in vitro and in vivo antitumor efficacy and toxicity T in vivo in an average and in mouse models of cancer tumors in humans with NMA as a contr in the comparison.
Materials and Methods Cell culture and were tested in vitro f All cells in Dulbecco’s modified Eagle’s medium containing 10% Fetal K Calf serum erg Was complements. MTT Briefly, cells were seeded in 96-well plates t and with AMN or NA Average for 72 hours. The medium was removed and the cells were treated with a L Solution, the 0.5 mg MTT / ml phosphate-buffered saline Solution incubated at 37 for 4 hours. The MTT-L Solution was removed and the cells were lysed with 100 l / well of dimethyl sulfoxide for 15 minutes at 37. The optical density was measured using a Bio-Rad Microplate Leseger t at 570 nm with DMSO as a blank. Triplicate wells were analyzed for each condition. The data were obtained by means of GraphPad Prism 5 software to the 50% inhibitory concentration. For the examination of DNA content, 1106 × treated cells were collected, with DNA-Prep Coulter Reagents Kit found Rbt to claim the manufacturer’s protocol and analyzed by FACS. The assays were performed on the apoptosis cells treated 2105 × Fnd Rbt with annexin V-Kit with fluorescein isothiocyanate and FACS was performed. Gene expression array of RNA isolated from HepG2 cells with 106 Q