Abstract |
The interaction of a newly designed benzocycloheptaindol-6-one derivative with DNA has been investigated by complementary spectroscopic techniques including absorption, circular and linear dichroism. Footprinting measurements were performed to delineate the sequence-selectivity of the drug- DNA interaction and a plasmid relaxation assay was used to study the effects of the drug on human DNA topoisomerases I and II. The results clearly indicated that the test compound behaves as a typical DNA intercalating agent but does not stimulate DNA cleavage by topoisomerases. At the cellular level, the cytometry measurements showed that the drug provoked a marked accumulation of HL60 human leukemia cells in the G2/M phase of the cell cycle. DNA is thus identified as a valid target for this new series of drugs particularly toxic to human (HL60) and murine ( P388) leukemia cells.
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Authors | J Benoit, S Routier, J Y Mérour, P Colson, C Houssier, C Bailly |
Journal | Anticancer research
(Anticancer Res)
2000 Sep-Oct
Vol. 20
Issue 5A
Pg. 3307-14
ISSN: 0250-7005 [Print] Greece |
PMID | 11062758
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Cycloheptanes
- DNA, Neoplasm
- DNA Topoisomerases, Type I
- DNA Topoisomerases, Type II
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Topics |
- Animals
- Antineoplastic Agents
(chemistry, pharmacology)
- Cell Cycle
- Cycloheptanes
(chemistry, pharmacology)
- DNA Topoisomerases, Type I
(metabolism)
- DNA Topoisomerases, Type II
(metabolism)
- DNA, Neoplasm
(drug effects)
- HL-60 Cells
- Humans
- Mice
- Molecular Conformation
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