A Strategy for Identifying Novel Inhibitors of DNA Topoisomerase I

Hecht, Sidney M.; Berry, David E.; MacKenzie, Laurie; Shultis, Elva A.; Chan, Jesse

doi:10.1007/978-1-4615-2610-0_5

Cited by 1 publication

(2 citation statements)

References 14 publications

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“…Because of their role in regulating DNA tertiary structures, topoisomerase are essential to cellular processes such as DNA replication, recombination, and gene transcription. They are the targets for many known compounds that affect DNA replication [142] as well as the targets for the design/ discovery of new antineoplastic agents [143,144]. Current clinical usage of the topoisomerase inhibitor topotecan (Hycamtin ® ) exemplifies the therapeutic potential of topoisomerase inhibitors [145].…”

Section: Topoisomerasesmentioning

confidence: 99%

“…Sakagami and coworkers have focused on the identification of topo I inhibitors from marine sources, using a primary bioassay that contains a camptothecin-resistant recombinant human topo I enzyme and the DNA substrate supercoiled plasmid pBR322 [144,146]. Bioassayguided fractionation has led to the isolation of two ceramide sulfates (topo I -IC 50 = 0.4 and 0.2 μM, respectively) from a Japanese collection of the bryozoan Watersipora cucullata [147], and a series of related amphimic acids from an Australian sponge of the genus Amphimedon (topo I -IC 50 s range from 0.47 to 6.7 μM) [146].…”

Section: Topoisomerasesmentioning

confidence: 99%

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Mechanism Targeted Discovery of Antitumor Marine Natural Products

Nagle¹,

Zhou²,

Mora³

et al. 2004

Current Medicinal Chemistry

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Antitumor drug discovery programs aim to identify chemical entities for use in the treatment of cancer. Many strategies have been used to achieve this objective. Natural products have always played a major role in anticancer medicine and the unique metabolites produced by marine organisms have increasingly become major players in antitumor drug discovery. Rapid advances have occurred in the understanding of tumor biology and molecular medicine. New insights into mechanisms responsible for neoplastic disease are significantly changing the general philosophical approach towards cancer treatment. Recently identified molecular targets have created exciting new means for disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance, and blood supply. Such tumor-specific treatments could someday decrease our reliance on traditional cytotoxicity-based chemotherapy and provide new less toxic treatment options with significantly fewer side effects. Novel molecular targets and state-of-the-art molecular mechanism-based screening methods have revitalized antitumor research and these changes are becoming an ever-increasing component of modern antitumor marine natural products research. This review describes marine natural products identified using tumor-specific mechanism-based assays for regulators of angiogenesis, apoptosis, cell cycle, macromolecule synthesis, mitochondrial respiration, mitosis, multidrug efflux, and signal transduction. Special emphasis is placed on natural products directly discovered using molecular mechanism-based screening.

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Section: Topoisomerasesmentioning

confidence: 99%