Plants and other living organisms represent valuable starting materials for the isolation of clinically efficacious anticancer agents. The mechanism of action of nearly all anticancer agents involves disrupting the normal physiological function of DNA, and many agents act by direct interaction. Thus, by utilizing this known target macromolecule, Naprotech currently proposes to devise methods for the detection and procurement of potential antitumor agents that function by this particular mechanism of action.In preliminary studies it has been established that HPLC methodology can be employed to detect substances in crude plant extracts that are capable of binding to DNA. A good correlation with cytotoxic potential was also found. With these and other plant extracts or pure compounds, Phase I studies will be performed to establish the general utility of this procedure for use as a prescreen or a method for detecting binding components in fractions obtained during purification schemes. Procedures will also be attempted to establish the feasibility of biospecifically extracting binding components from crude mixtures on the basis of DNA affinity. Experiments will be performed utilizing DNA coupled to cellulose and equilibrium dialysis. Quantitative aspects and the ability to recover bound substances will be studied. Success in these areas could ultimately lead to substantial savings in time and effort, and the rapid procurement of novel cytotoxic or antitumor agents from natural sources.National Cancer Institute (NCI)
