As a result of our previous investigations, antitumor compounds have been synthesized which are of interest to the NCI because of their clinical potential. Concurrently, we have obtained further support for our hypothesis concerning the mode of action of our thioxanthenones and xanthenones. We plan to test the generality of this mechanism which we call bio-oxidative alkylation which can be applied to ellipicines, m-AMSA and its analogues as well as bisinter-calating agents. Appropriate target molecules will be prepared in each group and these will be tested for their ability to bind to DNA and to act as antitumor agents. Since it has been found that HeLa cells bind irreversibly to hycanthone N-methylcarbamate and this drug inhibits the incorporation of uridine and thymidine, we plan to determine the exact locus of covalent binding between this drug and one of the bases in DNA and then RNA. If results are encouraging, the study will be expanded to include 7-hydroxyhycanthone N-methylcarbamate and other derivatives.
| 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 |
