A simplified hplc system is described for the detection of compounds capa-ble of binding to DNA. Compounds known to interact with DNA were found to invoke a positive response with this system, and the concentration-dependence and sensitivity were determined. When applied to 17 randomly selected plant extracts, five elicited a positive response and, of these, four were subsequently found to be cytotoxic with cultured KB or P-388 cells. As described in a companion paper, one of these extracts(derived from Albizia amara) has been further processed and found to contain a group of structurally-unique macrocyclic alkaloids that demonstrate a variety of biological activities. Therefore, this approach should prove of value in facilitating the identificationof plant extracts that contain substances capable of binding to DNA and the subsequent activity-directed fractionation for the procurement of active princi-ples. As a prescreen or monitor, these relatively uncomplicated hplc procedures can be used in laboratories not prepared to perform more complicated or costly bioassay techniques. Thus, the pool of potentially active novel chemical substances to beconsidered for more advanced testing could be increased.

The mechanism of several known antitumor and antimalarial agents involves interaction with DNA. Examples include alkylating agents (eg, chlorambucil, cyclophos-phamide, melphalan, streptozocin), antitumor antibiotics (eg, bleomycin, doxorubicin, mithramycin), and various other substances (eg, cisplatin, chloroquine). Based on the interaction of small molecular weight ligands withDNA, some short-term pro-cedures have been devised that are applicable for the discovery of naturally occurring agents that function by this mechanism (1-4). In addition, a variety of methods have been utilized for analyzing the interaction of small molecularweight compounds with DNA, such as equilibrium dialysis (5) and spectrophotometric titration (6). Employing size-exclusion hplc and the gravity-fed elution technique originally described by Hummel and Dreyer (7), we have devised a method for studying ligand-macromolecule (nucleic acid) interactions (8).