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Pan E, Oswald NW, Legako AG, et al. Precursor-Directed Generation of Amidine Containing Ammosamide Analogs: Ammosamides E-P. Chem Sci. 2013;4(1):482-488doi: 10.1039/C2SC21442C.
Pan, E., Oswald, N. W., Legako, A. G., Life, J. M., Posner, B. A., & Macmillan, J. B. (2013). Precursor-Directed Generation of Amidine Containing Ammosamide Analogs: Ammosamides E-P. Chemical science, 4(1), 482-488. https://doi.org/10.1039/C2SC21442C
Pan, Ende, et al. "Precursor-Directed Generation of Amidine Containing Ammosamide Analogs: Ammosamides E-P." Chemical science vol. 4,1 (2013): 482-488. doi: https://doi.org/10.1039/C2SC21442C
Pan E, Oswald NW, Legako AG, Life JM, Posner BA, Macmillan JB. Precursor-Directed Generation of Amidine Containing Ammosamide Analogs: Ammosamides E-P. Chem Sci. 2013 Jan;4(1):482-488. doi: 10.1039/C2SC21442C. PMID: 23209870; PMCID: PMC3510655.
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Chem Sci. 2013 Jan;4(1):482-488. doi: 10.1039/C2SC21442C.

Precursor-Directed Generation of Amidine Containing Ammosamide Analogs: Ammosamides E-P.

Chemical science

Ende Pan, Nathaniel W Oswald, Aaron G Legako, Janie M Life, Bruce A Posner, John B Macmillan

Affiliations

  1. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, USA.

PMID: 23209870 PMCID: PMC3510655 DOI: 10.1039/C2SC21442C

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 IC(50) values (0.4 to 0.8 μM).

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