A new topoisomerase-II inhibitor, BE-10988, produced by a streptomycete. I. Taxonomy, fermentation, isolation and characterization.

Oka, Hiroyuki; Yoshinari, Tomoko; Murai, Tetsuya; Kawamura, Kenji; Satoh, Fumio; Funaishi, Kohtaro; Okura, Akira; Suda, Hlroyuki; Okanishi, Masanori; Shizuri, Yoshikazu

doi:10.7164/antibiotics.44.486

Cited by 31 publications

(19 citation statements)

References 11 publications

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“…One example is the thiazolylindole BE-10988, which was isolated from the culture broth of Streptomyces sp. BA 10988 (Oka et al, 1991). It acts as DNA-topoisomerase inhibitor and restrains the growth of murine leukemia cell lines (Oka et al, 1991).…”

Section: Evolution Of Indolic Defence Compounds In Cruciferous Plantsmentioning

confidence: 99%

“…BA 10988 (Oka et al, 1991). It acts as DNA-topoisomerase inhibitor and restrains the growth of murine leukemia cell lines (Oka et al, 1991). Bacterial thiazole rings have been demonstrated to be incorporated from cysteine by non-ribosomal peptide synthetases (NRPS) (Crosa and Walsh, 2002), and this reaction may be involved also in BE-10988 biosynthesis.…”

Section: Evolution Of Indolic Defence Compounds In Cruciferous Plantsmentioning

confidence: 99%

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Evolution of camalexin and structurally related indolic compounds

Rauhut

Glawischnig

2009

Phytochemistry

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Section: Evolution Of Indolic Defence Compounds In Cruciferous Plantsmentioning

confidence: 99%

Section: Evolution Of Indolic Defence Compounds In Cruciferous Plantsmentioning

confidence: 99%

Evolution of camalexin and structurally related indolic compounds

Rauhut

Glawischnig

2009

Phytochemistry

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“…In essence, an anilide moiety may be considered a latent p ‐quinone system, since both oxygen atoms may be installed concomitantly using DMP. To demonstrate the applicability of this synthetic technology in complex molecule construction, the naturally occurring and biologically active substances epoxyquinomycin B ( 250 , Scheme )47 and BE‐10988 ( 254 , Scheme )48 were targeted for total synthesis.…”

Section: Mining the Gold: Discovery And Invention Of New Synthetimentioning

confidence: 99%

The CP Molecule Labyrinth: A Paradigm of How Endeavors in Total Synthesis Lead to Discoveries and Inventions in Organic Synthesis

Nicolaou¹,

Baran²

2002

Angew. Chem. Int. Ed.

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Imagine an artist carving a sculpture from a marble slab and finding gold nuggets in the process. This thought is not a far-fetched description of the work of a synthetic chemist pursuing the total synthesis of a natural product. At the end of the day, he or she will be judged by the artistry of the final work and the weight of the gold discovered in the process. However, as colorful as this description of total synthesis may be, it does not entirely capture the essence of the endeavor, for there is much more to be told, especially with regard to the contrast of frustrating failures and exhilarating moments of discovery. To fully appreciate the often Herculean nature of the task and the rewards that accompany it, one must sense the details of the enterprise behind the scenes. A more vivid description of total synthesis as a struggle against a tough opponent is perhaps appropriate to dramatize these elements of the experience. In this article we describe one such endeavor of total synthesis which, in addition to reaching the target molecule, resulted in a wealth of new synthetic strategies and technologies for chemical synthesis. The total synthesis of the CP molecules is compared to Theseus' most celebrated athlos (Greek for exploit, accomplishment): the conquest of the dreaded Minotaur, which he accomplished through brilliance, skill, and bravery having traversed the famous labyrinth with the help of Ariadne. This story from Greek mythology comes alive in modern synthetic expeditions toward natural products as exemplified by the total synthesis of the CP molecules which serve as a paradigm for modern total synthesis endeavors, where the objectives are discovery and invention in the broader sense of organic synthesis.

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“…The other systems shown in Figure 22 also stablise the cleavable complex but otherwise bear little resemblance to the APBIs. The pyrimido [1,6-a]benzimidazole [75] and benzimidazoquinazoline [76] [77,78] and AzaIQD [79] are both heterocyclic quinone-based DNA intercalating agents. The layout of BE 10988 is similar to that of the APBIs, and one can envisage alterations within the context of the APBI structure, i.e., acetylation of the 5-amino group to afford an amide and benzimidazole functionalisation.…”

Section: Review Of the Patent Literature; Benzimidazole-based Topoisomentioning

confidence: 99%

Pyrrolobenzimidazoles in cancer treatment

Skibo¹

1998

Expert Opinion on Therapeutic Patents

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This review presents a discussion of the design, chemistry, cytotoxicity and antitumour activity of agents based on the pyrrolobenzimidazole or azomitosene ring system. The focus is the 6-aziridinylquinone derivatives (PBIs) and 6-acetamidoquinone derivatives (APBIs) of this ring system (see Figure 1). Comparisons will be made with related benzimidazole and indole-based antitumour agent systems reported in the patent literature. The pyrrolobenzimidazoles will be shown to represent a new and useful class of antitumour agent with advantages over other such agents. The 6-aziridinyl derivatives (PBIs) alkylate and cleave DNA upon two-electron reduction as a result of phosphate alkylation by the protonated aziridine ring. In contrast, the 6-acetamido quinone derivatives (APBIs) do not require reductive activation to exert cytotoxicity. The 6-acetamido quinone derivatives act as DNA intercalating agents and inhibit the first step of topoisomerase II-mediated DNA relaxation. Some PBIs were found to exhibit high toxicity in mice with minimal antitumour activity while others exhibit a high degree of tumour selectivity. The APBIs showed significant increases in lifespans of mice as well as activity against tumours distant from the injection site.

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A new topoisomerase-II inhibitor, BE-10988, produced by a streptomycete. I. Taxonomy, fermentation, isolation and characterization.

Cited by 31 publications

References 11 publications

Evolution of camalexin and structurally related indolic compounds

Evolution of camalexin and structurally related indolic compounds

The CP Molecule Labyrinth: A Paradigm of How Endeavors in Total Synthesis Lead to Discoveries and Inventions in Organic Synthesis

Pyrrolobenzimidazoles in cancer treatment

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