Abstract:
Topoisomerase I is an important therapeutic target in cancer chemotherapy. We are interested in the continuing discovery of new topoisomerase I-targeted agents from Thai medicinal plants with previously reported as cytotoxicity by using Yeast cell-based assay. The transformant yeast containing Arabidopsis thaliana topoisomerase I gene was developed to achieve controllable expression of the topoisomerase I enzyme. From the screening of 27 Thai medicinal plants, 6 ethanolic plant-part extracts; root and leaf of Rhinacanthus nasutus, whole plant of Grangea maderaspatana, caudex of Stephania suberosa, rhizome of Curcuma longa and rhizome of Curcuma zedoaria, showed inhibitory activities of enzyme topoisomerase I. The extract of G. maderaspatana was selected for further study to determine the bioactive compounds since it has never been reported for its topoisomerase I inhibitory activity before. Bioassay-guided fractionation from whole plant of G. maderaspatana by yeast cell– based assay led to the identification of two bioactive compounds. They are sesquiterpene lactone namely, (-)-frullanolide and (-)-7α-hydroxyfrullanolide. Their structures were determined by spectroscopic methods and compared with previous reports. These compounds exhibited topoisomerase I inhibitory activities by yeast cell-based assay. They also processed in vitro anti-cancer activities against human cell lines, KB oral cavity cancer, MCF-7 breast cancer, and NC-H187 small lung cancer. This is the first report of cytotoxicity due to topoisomerase I inhibitory mechanism of two compounds from G. maderaspatana.
