Cytotoxicity of cobalt complexes of furan oximes in murine and human tissue-cultured cell lines

Citation
Ih. Hall et al., Cytotoxicity of cobalt complexes of furan oximes in murine and human tissue-cultured cell lines, APPL ORGAN, 13(11), 1999, pp. 819-828
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry
Journal title
APPLIED ORGANOMETALLIC CHEMISTRY
ISSN journal
0268-2605 → ACNP
Volume
13
Issue
11
Year of publication
1999
Pages
819 - 828
Database
ISI
SICI code
0268-2605(199911)13:11<819:COCCOF>2.0.ZU;2-B
Abstract
The copper complexes of 2-furaldehyde and furan oximes have previously demo nstrated potent cytotoxicity, L1210 DNA synthesis inhibition, DNA topoisome rase II inhibition and DNA fragmentation. Currently a series of cobalt meta l complexes of 2-furaldehyde oximes were compared with copper complexes of furan oximes to determine whether the type of metal is important to the cyt otoxicity and mode of action of the complexes. The cobalt complexes of fura n oximes, like the copper complexes, were shown to be cytotoxic to suspende d tumor cell lines, e.g. leukemias, lymphomas, acute monocytic leukemia and HeLa-S-3 uterine carcinoma. The cobalt complexes did not demonstrate drama tic cytotoxicity against the growth of tumors derived from solid human tumo r lines. The cobalt complexes preferentially inhibited L1210 DNA synthesis, followed by inhibition of RNA and protein synthesis from 25 to 100 mu M ov er 60 min. These agents, like the copper complexes of 2-furaldehyde and fur an oximes, were inhibitors of DNA polymerase ct activity and de novo purine synthesis with marginal inhibition of ribonucleoside reductase and dihydro folate reductase activities with DNA fragmentation. Unlike the copper compl exes, the cobalt complexes did not inhibit L1210 DNA topoisomerase II activ ity but did reduce thymidylate synthetase activity. Thus, varying the type of metal within the complexes of 2-furaldehyde and furan oximes produces di fferences in both cytotoxicity and mode of action. Copyright (C) 1999 John Wiley & Sons, Ltd.