Title

Modeling The Preferred Shapes Of Polyamine Transporter Ligands And Dihydromotuporamine-C Mimics: Shovel Versus Hoe

Abstract

Preferred conformers generated from motuporamine and anthracene-polyamine derivatives provided insight into the shapes associated with polyamine transporter (PAT) recognition and potentially dihydromotuporamine C (4a) bioactivity. Molecular modeling revealed that N1-(anthracen-9- ylmethy)-3,3-triamine (6a), N1-(anthracen-9-ylmethyl)-4,4-triamine (6b), N1-(anthracen-9-ylmethyl)-N1-ethyl-3,3-triamine (7a), N1-(anthracen-9-ylmethyl)-N1-ethyl-4,4-triamine (7b), and 4a all preferred a hoe motif. This hoe shape was defined by the all-anti polyamine shaft extending above the relatively flat, appended ring system. The hoe geometry was also inferred by the 1H NMR spectrum of the free amine of 7a (CDCl3), which showed a strong shielding effect of the anthracene ring on the chemical shifts associated with the appended polyamine chain. This shielding effect was found to be independent over a broad concentration range of 7a, which also supported an intramolecular phenomenon. The degree of substitution at the N1-position seems to be an important determinant of both the molecular shape preferences and biological activity of anthracenylmethyl-polyamine conjugates. © 2006 American Chemical Society.

Publication Date

4-20-2006

Publication Title

Journal of Medicinal Chemistry

Volume

49

Issue

8

Number of Pages

2407-2416

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/jm050814w

Socpus ID

33646109581 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/33646109581

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