Planta Med 2008; 74 - PB158
DOI: 10.1055/s-0028-1084502

Isolation of Puupehenone analogs and further development of the structure activity relationship within this compound class

SJ Robinson 1, M Riener 1, K Tenney 1, ST Loveridge 1, SL Mooberry 2, FA Valeriote 3, P Crews 1
  • 1Department of Chemistry and Biochemistry and Institute for Marine Sciences, University of California, Santa Cruz, CA USA 95064.
  • 2Southwest Foundation for Biomedical Research, San Antonio, TX, USA 78245.
  • 3Josephine Ford Cancer Center, Henry Ford Health System, Detroit, MI USA 48202

One aim of the 2005 Papua New Guinea expedition was collection of Hyrtios, a sponge that has been a rich source of bioactive metabolites. This was successful and the Hyrtios sp. (05409) obtained was extracted and initially showed activity in both solid tumor selectivity and histone deacetylase inhibition (HDACi) assays. Separation to identify active compounds began using the Gilson peak library generation technology in-line with ESIMS and ELSD guided collection of fractions. Each 200 milligram injection resulted in reproducible separation with sufficient material in each fraction for further biological and analytical analysis. HDACi activity was confirmed using both in-house (BIOMOL Research Laboratories, Inc., Plymouth Meeting, PA) and collaborative assays. HDACi was compared between puupehenone [1] and puupehenone analog monomers and dimers and a preliminary structure-activity relationship was established. Puupehenone, a known sponge metabolite, was the major component of this extract having an HDACi IC50=3µg/mL.

References: 1a) Scheuer, P. J. (1979) Pure Appl. Chem. 51:1893–1900. b) Capon, R. J. (1996)J. Nat. Prod. 59: 900–901