clerocidin and Leukemia-P388

Topoisomerase II is now viewed as an important cellular target of antitumor drugs including both DNA intercalators (m-AMSA, ellipticine and Adriamycin) and the nonintercalator epipodophyllotoxin derivatives (VP-16 and VM-26). Topoisomerase I is also shown to be the cellular target of camptotecin. These drugs targeting topoisomerase have been used to establish a relationship between drug-induced cleavable complex formation and cytotoxicity. Mechanistically oriented screening based on the identification of these chemotherapeutic targets have identified a number of antitumor agents that induce topoisomerases mediated DNA cleavage. The new antitumor drugs targeting topoisomerases are reviewed.

Topics: Amsacrine; Animals; Antibiotics, Antineoplastic; Diterpenes; DNA Topoisomerases, Type II; Doxorubicin; Etoposide; Leukemia P388; Mice

A number of strains of Oidiodendron truncatum was shown to produce a new antibiotic, PR-1350, which was isolated in the form of an amorphous powder either directly or via a crystalline monomethanolate, PR-1381, which in solution is reconverted to the parent compound. The antibiotic inhibits a broad spectrum of Gram-positive and Gram-negative bacteria in vitro, and has been shown to be active against P-388 lymphocytic leukemia in mice. Biosynthetic considerations based on the results of [1-13C]acetate incorporation indicate that the antibiotic is a diterpene of the clerodane type.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Diterpenes; Drug Evaluation, Preclinical; Fermentation; Leukemia P388; Mice; Microbial Sensitivity Tests; Mitosporic Fungi; Species Specificity