Title

Synthesis And Biological Evaluation Of N1-(Anthracen-9-Ylmethyl)Triamines As Molecular Recognition Elements For The Polyamine Transporter

Abstract

An efficient modular synthesis of N1-substituted triamines containing different tether lengths between nitrogen centers was developed. A series of N1-(9-anthracenylmethyl)triamines were evaluated for biological activity in L1210 (murine leukemia), α-difluoromethylornithine (DFMO)treated L1210, Chinese hamster ovary (CHO), and CHO-MG cell lines. All triamines 8 had increased potency in DFMO-treated L1210 cells. The 4,4- and 5,4-triamine systems had the highest affinity for the polyamine transporter (PAT) with L1210 Ki values of 1.8 and 1.7 μM, respectively. This trend was also reflected in the CHO studies. Surprisingly, the respective 4,4- and 5,4-triamine systems had 150-fold and 38-fold higher cytotoxicity in CHO cells containing active polyamine transporters. Initial microscopy studies revealed the rapid formation of vesicular structures within A375 melanoma cells treated with the N1-(9- anthracenylmethyl)homospermidine (4,4-triamine) conjugate. In summary, the 4,4- and 5,4-triamines were identified as selective vector motifs to ferry anthracene into cells via the PAT.

Publication Date

6-19-2003

Publication Title

Journal of Medicinal Chemistry

Volume

46

Issue

13

Number of Pages

2663-2671

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/jm030028w

Socpus ID

0038240603 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/0038240603

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