Planta Med 2008; 74 - PB172
DOI: 10.1055/s-0028-1084516

Ammosamides A and B new cytotoxic alkaloids isolated from a marine Streptomyces sp

SP Gaudêncio 1, JB MacMillan 1, PR Jensen 1, W Fenical 1
  • 1Scripps Institutions of Oceanography, Center for Marine Biotechnology and Biomedicine, University of California at San Diego, La Jolla, CA 92093–0204 USA

The marine environment has now been shown to be a new source for novel actinomycete bacteria, which are the most economically and biotechnologically valuable bacteria for the discovery of novel bioactive secondary metabolites [1,2]. Here we report the discovery of Ammosamides A (1) and B (2), which include the first example of a natural product bearing a thiolactam ring. These compounds were isolated from a Streptomyces strain collected from a mud sample collected in the Bahamas Islands in 2001.

It appears that the alkaloids 1 and 2 are derived biosynthetically from tryptophan followed by a variety of oxidative transformations. The new compounds exhibited potent activity (ca. 200 nM) against HCT-116 and other lines of tumor cells. Studies now in progress show that the ammosamides have a unique intracellular target and may represent a new class of agents worth of preclinical development.

Acknowledgements: Financial support provided by NIH (NCI under grant CA44848). Susana P. Gaudêncio thanks the Fundação para a Ciência e Tecnologia, Portugal for a postdoctoral fellowship (SFRH/BPD/23966/2005).

References: 1. Fenical W., Jensen P. R. (2006) Nat. Chem Biol. 2: 666–673. 2. Berdy J. (2005)J Antibiot. (Tokyo) 58: 1–26.