IDENTIFICATION OF NOVEL TOPOISOMERASE INHIBITORS

PLANT EXTRACTS AND TRADITIONAL MEDICINES HAVE LONG BEEN THOUGHT TO CONTAIN BIOACTIVE MOLECULES CAPABLE OF ELICITING A THERAPEUTIC RESPONSE. HOWEVER, THE POTENTIAL UTILITY OR MODE OF ACTION OF THESE NATURAL PRODUCTS HAS NOT BEEN EFFECTIVELY STUDIED IN WESTERN SCIENTIFIC RESEARCH. RECENT ADVANCES IN THE MOLECULAR UNDERSTANDING OF DRUG ACTION WILL BE EMPLOYED IN PHASE I IN AN EFFORT TO IDENTIFY AND FURTHER EVALUATE THE BIOACTIVITY OF NATURAL PRODUCTS. PLANT EXTRACTS AND TRADITIONAL MEDICINES WILL BE ANALYZED IN A HIGH-THROUGHPUT BIOCHEMICAL ASSAY FOR THEIR ABILITY TO INHIBIT TOPOISOMERASE ACTIVITY IN TRANSFORMED CELL LINES. BECAUSE TOPOISOMERASES HAVE BEEN IDENTIFIED AS THE PRIMARY TARGET OF SOME OF THE MOST POPULAR ANTINEOPLASTIC DRUGS CURRENTLY IN USE, THIS ASSAY WOULD IDENTIFY NATURAL PRODUCTSTHAT WOULD ULTIMATELY BE DEVELOPED INTO NOVEL ANTICANCER AGENTS. THE ABILITY OF LEAD COMPOUNDS TO INHIBIT TOPOISOMERASE ACTIVITY IN VITRO USING PURIFIED TOPOISOMERASE I AND II, AS WELL AS THEIR ABILITY TO INHIBIT THE GROWTH IN TRANSFORMED CELLS IN VITRO, WILL ALSO BE EVALUATED. PROMISING LEAD COMPOUNDS WOULD BE FURTHER PURIFIED AND DEVELOPED AS ANTICANCER AGENTS IN PHASE II.