Linked Life Data

11405653

Source:http://linkedlifedata.com/resource/pubmed/id/11405653

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2001-6-14
pubmed:abstractText
A series of thiosemicarbazones (TSCs) (bearing a (4)N-azabicyclo[3.2.2]nonane moiety) derived from 3-acylpyridazines, 4-acetylpyrimidines, and 2-acetylpyrazines (1-8) were synthesized as potential antitumor agents. TSCs 1-8 exhibited potent cytotoxic activity against human acute lymphoblastic leukemia CCRF-CEM cells (IC(50) = 0.05-0.77 microM) and colon adenocarcinoma HT-29 cells (IC(50) = 0.011-2.22 microM). Copper II complexes of TSCs 1-8 showed significant improvement in cytotoxic activity against HT-29 cells (IC(50) = 0.004-1.51 microM) by a factor of 3. However, complexation of ligands 1, 2, 4, and 6 with Fe(II) results in lowering of cytotoxic activity by a factor of approximately 7. In clonogenic assays involving human tumor cells of different tumor origins, compounds 5, 7, 8, and their copper complexes 5Cu(II), 7Cu(II), and 8Cu(II) exhibited remarkable cytotoxic activities with mean IC(50) values of 6, 0.18, 1, 1, 0.37, and 0.37 nM, respectively. In particular, the compounds were highly effective against human colon carcinoma and large and small cell lung carcinoma cells. The TSC derivative 5 was evaluated in vivo in nude mice bearing LXFL 529 human large cell lung carcinoma cells. With respect to antitumor activity, application of 30 mg/kg/d resulted in moderate inhibition (42%) of tumor growth. No effect on tumor growth was observed at a dose of 10 mg/kg/d. However, a dose of 40 or 60 mg/kg/d resulted in 50 and 75% death, respectively, in the treated mice, indicating the high toxicity of these compounds. Using human liver microsomes, compound 5 was found to be rapidly and highly metabolized in vitro. In actual fact, only 2% of the unmetabolized compound could be detected in the incubation medium after 5 min. The IC(50) for cell proliferation (0.006-0.022 microM) elicited by these compounds is much lower than that of the inhibition of [(14)C]cytidine incorporation into DNA (0.18-3.32 microM). These compounds are also noncell cycle specific agents. Interestingly, compounds 5, 5Cu(II), and 8 were found to be potent inducers of apoptosis in Burkitt's lymphoma cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2164-71
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11405653-Antineoplastic Agents, pubmed-meshheading:11405653-Apoptosis, pubmed-meshheading:11405653-Body Weight, pubmed-meshheading:11405653-Burkitt Lymphoma, pubmed-meshheading:11405653-Carcinoma, Large Cell, pubmed-meshheading:11405653-Cell Cycle, pubmed-meshheading:11405653-Colony-Forming Units Assay, pubmed-meshheading:11405653-Copper, pubmed-meshheading:11405653-Cytidine, pubmed-meshheading:11405653-Drug Screening Assays, Antitumor, pubmed-meshheading:11405653-Humans, pubmed-meshheading:11405653-Iron, pubmed-meshheading:11405653-Lung Neoplasms, pubmed-meshheading:11405653-Microsomes, Liver, pubmed-meshheading:11405653-Neoplasm Transplantation, pubmed-meshheading:11405653-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:11405653-Thiosemicarbazones, pubmed-meshheading:11405653-Tumor Cells, Cultured, pubmed-meshheading:11405653-Tumor Stem Cell Assay
pubmed:year
2001
pubmed:articleTitle
Synthesis, cytotoxicity, and antitumor activity of copper(II) and iron(II) complexes of (4)N-azabicyclo[3.2.2]nonane thiosemicarbazones derived from acyl diazines.
pubmed:affiliation
Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria. Johnny.Easmon@uibk.ac.at
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't