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Issue 1, 2013
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Precursor-directed generation of amidine containing ammosamide analogs: ammosamides E–P

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Abstract

Ammosamides E–F (1–2), are amidine analogs of the ammosamide family of alkaloids isolated from a marine-derived Streptomyces variabilis. Further studies with S. variabilis revealed a variety of aryl and alkyl amines added into the fermentation media could be efficiently incorporated into the ammosamide framework to generate a library of precursor-directed amidine analogs, ammosamides G–P (9–18). We demonstrate that the amines are introduced via non-enzymatic addition to the iminium ion of ammosamide C. Biological evaluation of the amidine analogs against quinone reductase 2 (QR2) showed low nM potency for a number of analogs. When tested for in vivo activity against a panel of non-small cell lung cancer (NSCLC) cell-lines there was a clear increase in potency by incorporation of lipophilic alkylamines, with the most potent compounds having sub μM IC50 values (0.4 to 0.8 μM).

Graphical abstract: Precursor-directed generation of amidine containing ammosamide analogs: ammosamides E–P

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Publication details

The article was received on 05 Sep 2012, accepted on 08 Oct 2012 and first published on 08 Oct 2012


Article type: Edge Article
DOI: 10.1039/C2SC21442C
Citation: Chem. Sci., 2013,4, 482-488
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    Precursor-directed generation of amidine containing ammosamide analogs: ammosamides E–P

    E. Pan, N. W. Oswald, A. G. Legako, J. M. Life, B. A. Posner and J. B. MacMillan, Chem. Sci., 2013, 4, 482
    DOI: 10.1039/C2SC21442C

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