Precursor-directed generation of amidine containing ammosamide analogs: Ammosamides E-P

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

Research output: Contribution to journalArticle

48 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)482-488
Number of pages7
JournalChemical Science
Volume4
Issue number1
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Chemistry(all)

Fingerprint Dive into the research topics of 'Precursor-directed generation of amidine containing ammosamide analogs: Ammosamides E-P'. Together they form a unique fingerprint.

  • Cite this