Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target

Malcolm S Buchanan; Anthony R Carroll; Gregory A Fechner; Anthony Boyle; Moana M Simpson; Rama Addepalli; Vicky M Avery; John N A Hooper; Nancy Su; Huawei Chen; Ronald J Quinn

doi:10.1016/j.bmcl.2007.10.021

Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6860-3. doi: 10.1016/j.bmcl.2007.10.021. Epub 2007 Oct 16.

Authors

Malcolm S Buchanan¹, Anthony R Carroll, Gregory A Fechner, Anthony Boyle, Moana M Simpson, Rama Addepalli, Vicky M Avery, John N A Hooper, Nancy Su, Huawei Chen, Ronald J Quinn

Affiliation

¹ Eskitis Institute, Griffith University, Brisbane, Qld 4111, Australia.

PMID: 17964784
DOI: 10.1016/j.bmcl.2007.10.021

Abstract

Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening campaign was conducted to discover inhibitors of Icmt. The Australian marine sponge, Pseudoceratina sp., yielded spermatinamine, a novel alkaloid with a bromotyrosyl-spermine-bromotyrosyl sequence, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of Icmt.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / toxicity*
Biological Products / chemistry*
Biological Products / toxicity*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / toxicity
Magnetic Resonance Spectroscopy
Molecular Structure
Neoplasms / enzymology*
Neoplasms / pathology
Protein Methyltransferases / antagonists & inhibitors*
Protein Methyltransferases / metabolism
Spermine / analogs & derivatives*
Spermine / chemistry
Spermine / toxicity
Tyrosine / analogs & derivatives*
Tyrosine / chemistry
Tyrosine / toxicity

Substances

Antineoplastic Agents
Biological Products
Enzyme Inhibitors
spermatinamine
Spermine
Tyrosine
Protein Methyltransferases
protein-S-isoprenylcysteine O-methyltransferase