Antitumor agents--CLI. Bis(helenalinyl)glutarate and bis(isoalantodiol-B)glutarate, potent inhibitors of human DNA topoisomerase II.

Evaluation of a number of cytotoxic antitumor sesquiterpene lactones and their derivatives has led to the discovery of bis(helenalinyl)glutarate (4) and bis(isoalantodiol-B)glutarate (10) as potent inhibitors of human-derived topoisomerase II. Unlike etoposide, which inhibits by preventing the DNA rejoining process, compounds 4 and 10 inhibit topoisomerase II without causing DNA breakage. The structure-activity relationships of 4, 10, and related compounds are discussed.