Abstract

A mechanism of action to account for the antitumor activity and cytotoxicity of certain drugs was proposed which was termed bio- oxidative alkylation. This hypothesis has led to the design of new potential antitumor agents in the ellipticine and olivacine series. The mechanism of action was partially confirmed in the case of hycanthone and the precise mode of activity of it and an analog of ellipticine will be studied further. It is suggested that these drugs are involved in the irreversible interaction with the mammalian DNA Topoisomerase II-DNA complex and that this is the cytotoxic event. Experiments are suggested to test the validity of this hypothesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA019674-10A1
Application #
3165186
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1977-05-01
Project End
1991-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Rensselaer Polytechnic Institute
Department
Type
Schools of Arts and Sciences
DUNS #
002430742
City
Troy
State
NY
Country
United States
Zip Code
12180

  Publications

Archer, S; Pica-Mattoccia, L; Cioli, D et al. (1988) Preparation and antischistosomal and antitumor activity of hycanthone and some of its congeners. Evidence for the mode of action of hycanthone. J Med Chem 31:254-60
Archer, S; Ross, B S; Pica-Mattoccia, L et al. (1987) Synthesis and biological properties of some 6H-pyrido[4,3-b]carbazoles. J Med Chem 30:1204-10