Amino Acid/Spermine Conjugates:  Polyamine Amides as Potent Spermidine Uptake Inhibitors

• Published in: Journal of medicinal chemistry Vol. 44; no. 22; pp. 3632 - 3644
• Main Authors: Burns, Mark R, Carlson, C. Lance, Vanderwerf, Scott M, Ziemer, Josh R, Weeks, Reitha S, Cai, Feng, Webb, Heather K, Graminski, Gerard F
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.10.2001; Amer Chemical Soc
• Subjects: Amino Acids - chemistry; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biological Transport; Chemistry, Medicinal; Drug Interactions; Drug Screening Assays, Antitumor; Eflornithine - pharmacology; General aspects; Humans; Life Sciences & Biomedicine; Lysine - analogs & derivatives; Lysine - chemical synthesis; Lysine - pharmacology; Medical sciences; Ornithine Decarboxylase Inhibitors; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Putrescine - metabolism; Science & Technology; Spermidine - antagonists & inhibitors; Spermidine - metabolism; Spermine - analogs & derivatives; Spermine - chemical synthesis; Spermine - metabolism; Spermine - pharmacology; Structure-Activity Relationship; Tumor Cells, Cultured; PUTRESCINE TRANSPORT; TRANSPORT INHIBITORS; ESCHERICHIA-COLI; GASTROINTESTINAL-TRACT; GROWTH; SPIDER TOXIN; HIGH-AFFINITY; HUMAN FIBROBLASTS; L1210 LEUKEMIA-CELLS; MAMMALIAN-CELLS; Antineoplastic agent; Human; Polyamine; Aminoamide; Cytotoxicity; Epithelium; In vitro; α-Aminoacid; Cell line; Functionalization; Structure activity relation; Spermidine; Carboxamide; Mammary gland; Inhibition; Conjugated compound; Chemical synthesis; Tumor cell; Carrier protein

In this paper we describe the synthesis and characterization of a series of simple spermine/amino acid conjugates, some of which potently inhibit the uptake of spermidine into MDA-MB-231 breast cancer cells. The presence of an amide in the functionalized polyamine appeared to add to the affinity for...