DNA as an affinity probe useful in the detection and isolation of biologically active natural products.
A simplified hplc system is described for the detection of compounds capable 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 a value in facilitating the identification of plant extracts that contain substances capable of binding to DNA and the subsequent activity-directed fractionation for the procurement of active principles. 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 be considered for more advanced testing could be increased.
Pezzuto
J M
JM
Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, Univeristy of Illinois, Chicago 60612.
Che
C T
CT
McPherson
D D
DD
Zhu
J P
JP
Topcu
G
G
Erdelmeier
C A
CA
Cordell
G A
GA
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004247:DNA; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D015335:Molecular Probes; D010936:Plant Extracts / Q000302:isolation & purification* / Q000494:pharmacology; D012343:RNA, Transfer; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015335:Molecular Probes; D010936:Plant Extracts; D004247:DNA; D012343:RNA, Transfer