A New Antibiotic, Kinamycin

Ito, Shinya; Matsuya, T; Ōmura, Satoshi; Otani, Motoyasu; Nakagawa, Akira

doi:10.7164/antibiotics.23.315

Cited by 117 publications

(45 citation statements)

References 4 publications

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“…432–439 Initial structural characterization incorrectly assigned the kinamycins as N-cyanocarbazoles. 439–441 It was only after two decades of investigations that the molecules were reassigned as the correct 5-diazobenzo[b]fluorenes.…”

Section: N–n Bond Forming Enzymesmentioning

confidence: 99%

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

et al. 2017

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Natural products that contain functional groups with heteroatom-heteroatom linkages (X–X, where X = N, O, S, and P) are a small yet intriguing group of metabolites. The reactivity and diversity of these structural motifs has captured the interest of synthetic and biological chemists alike. Functional groups containing X–X bonds are found in all major classes of natural products and often impart significant biological activity. This review presents our current understanding of the biosynthetic logic and enzymatic chemistry involved in the construction of X–X bond containing functional groups within natural products. Elucidating and characterizing biosynthetic pathways that generate X–X bonds could both provide tools for biocatalysis and synthetic biology, as well as guide efforts to uncover new natural products containing these structural features.

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Section: N–n Bond Forming Enzymesmentioning

confidence: 99%

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

et al. 2017

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“…This structural change diminishes cytotoxicity by two orders of magnitude. 2 The kinamycins [e.g., (–)-kinamycin C ( 3 )] 4–8 were isolated in the early 1970s and are the first natural products found to contain a diazofluorene (for reviews, see refs. 9–13).…”

mentioning

confidence: 99%

The cytotoxicity of (−)-lomaiviticin A arises from induction of double-strand breaks in DNA

et al. 2014

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The metabolite (–)-lomaiviticin A, which contains two diazotetrahydrobenzo[b]fluorene (diazofluorene) functional groups, inhibits the growth of cultured human cancer cells at nanomolar–picomolar concentrations; however, the mechanism responsible for the potent cytotoxicity of this natural product is not known. Here we report that (–)-lomaiviticin A nicks and cleaves plasmid DNA by an ROS- and iron-independent pathway and that the potent cytotoxicity of (–)-lomaiviticin A arises from induction of DNA double-strand breaks (dsbs). In a plasmid cleavage assay, the ratio of single-strand breaks (ssbs) to dsbs is 5.3±0.6:1. Labeling studies suggest this cleavage occurs via a radical pathway. The structurally related isolates (–)-lomaiviticin C and (–)-kinamycin C, which contain one diazofluorene, are demonstrated to be much less effective DNA cleavage agents, thereby providing an explanation for the enhanced cytotoxicity of (–)-lomaiviticin A compared to other members of this family.

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“…B. Kinamycin C (11, Abbildung 13)] sind eine Gruppe antibakterieller Agentien, die 1970 von Omura et al entdeckt wurden. [95] Sie wirken stark gegen Gram-positive Bakterien, und Kinamycin C weist zudem eine bescheidene Cytotoxizität auf. Auf der Basis von Röntgen-strukturanalysen und chemischen Argumenten wurde für Kinamycin C ursprünglich Struktur 168 postuliert, die eine Cyanamideinheit enthält (Abbildung 13).…”

Section: Kinamycin Cunclassified

Fortschritte in der Chemie und Biologie natürlicher Antibiotika

et al. 2009

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Seit der bahnbrechenden Entdeckung von Penicillin wurde die Vielfalt natürlich vorkommender Moleküle ausgiebig hinsichtlich ihrer Eignung als Medikamente sowie zum Auffinden neuer Leitstrukturen beim Wirkstoffdesign untersucht. Die Suche nach Wirkstoffen, mit denen Infektionskrankheiten bekämpft werden können, war dabei von besonderem Interesse und verlief sehr erfolgreich. Die Erforschung der Antibiotika weist eindrucksvolle Entdeckungen und Geschichten über die Entwicklung von Wirkstoffen auf, von denen die große Mehrheit ihren Ursprung in Naturstoffen hat. Die Chemie und besonders die chemische Synthese haben eine bedeutende Rolle dabei gespielt, natürlich vorkommende Antibiotika und deren Derivate für die medizinische Anwendung bereitzustellen, und zweifellos werden diese Disziplinen auch künftig Schlüsseltechnologien sein. In dieser Übersicht stellen wir einige der bedeutendsten neueren Entwicklungen und Fortschritte in der Chemie, Biologie und Medizin natürlich vorkommender Antibiotika vor, wobei die Totalsynthese, das Design von Analoga und die biologische Bewertung von Molekülen mit neuartigen Wirkmechanismen im Vordergrund stehen.

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A New Antibiotic, Kinamycin

Cited by 117 publications

References 4 publications

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

The cytotoxicity of (−)-lomaiviticin A arises from induction of double-strand breaks in DNA

Fortschritte in der Chemie und Biologie natürlicher Antibiotika

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