Title

Synthesis and biological evaluation of dihydromotuporamine derivatives in cells containing active polyamine transporters

Authors

Authors

N. Kaur; J. G. Delcros; N. Martin;O. Phanstiel

Comments

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Abbreviated Journal Title

J. Med. Chem.

Keywords

RING-CLOSING-METATHESIS; XESTOSPONGIA-EXIGUA KIRKPATRICK; MAMMALIAN-CELLS; MOLECULAR REQUIREMENTS; PROTONATION CONSTANTS; SELECTIVE DELIVERY; NUCLEIC-ACIDS; SPERMIDINE; ANALOGS; MOTUPORAMINES; Chemistry, Medicinal

Abstract

Dihydromotuporamine C (4) and its 4,4-triamine analogue (5) were synthesized in good yield using ring-closing metathesis (RCM) methods. Comparison of their biological activities (K-i determinations in L1210 cells and IC50 determinations in L1210, CHO, and CHO-MG cells) revealed that the motuporamine derivatives do not use the polyamine transporter (PAT) for cellular entry. Bioevaluation of a N-1-(anthracen-9-ylmethyl)-N-1-(ethyl)homospermidine control (7) revealed that the presence of a N-1 tertiary amine center imparted a significant reduction in the PAT affinity of the polyamine conjugate and abolished its PAT-targeting selectivity.

Journal Title

Journal of Medicinal Chemistry

Volume

48

Issue/Number

11

Publication Date

1-1-2005

Document Type

Article

Language

English

First Page

3832

Last Page

3839

WOS Identifier

WOS:000229443700021

ISSN

0022-2623

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