topopyrone-c and Lung-Neoplasms

A series of structurally simple analogues of natural topopyrone C were synthesized and tested for cytotoxic and topoisomerase I inhibitory activities. The removal of the hydroxyl groups at the 5 and 9 positions resulted in an increased cytotoxic potency and ability to stabilize topoisomerase-mediated cleavage. In addition, the results suggest that some structural features, such as the pyrone ring and a polar group in position 11, are fundamental for topoisomerase I inhibitory effect. These structural requirements are also consistent with the cytotoxic activity.

Topics: Anthraquinones; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; DNA; DNA Topoisomerases, Type I; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Lung Neoplasms; Pyrones; Structure-Activity Relationship; Topoisomerase I Inhibitors