Title

A Comparison Of Chloroambucil- And Xylene-Containing Poly Amines Leads To Improved Ligands For Accessing The Polyamine Transport System

Abstract

Several disubstituted arylene- and chloroambucil-polyamine conjugates were synthesized and evaluated for their ability to target cells via their polyamine transport system (PAT). As compared to the monosubstituted analogues, the disubstituted arylene systems were superior PAT targeting agents. Using a Chinese hamster ovary (CHO) cell line (PAT active) and its CHO-MG mutant (PAT inactive), the series was screened for their PAT targeting ability. The data were expressed as a CHOMG/CHO IC50 ratio. Indeed, the disubstituted systems gave high IC50 ratios (e.g., ratio > 2000), which indicated high selectivity for the PAT. The chloroambucil adducts were less toxic than the corresponding arylmethyl compounds. In this regard, having the proper recognition element (i.e., homospermidine) and cytotoxic "cargo" were deemed paramount for successful drug delivery via the PAT. © 2008 American Chemical Society.

Publication Date

3-13-2008

Publication Title

Journal of Medicinal Chemistry

Volume

51

Issue

5

Number of Pages

1393-1401

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/jm070794t

Socpus ID

41649098451 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/41649098451

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