Synthesis of spermidine and norspermidine dimers as high affinity polyamine transport inhibitors

被引:26
作者
Covassin, L
Desjardins, M
Charest-Gaudreault, R
Audette, M
Bonneau, MJ
Poulin, R [1 ]
机构
[1] Univ Laval, Fac Med, Dept Physiol, Quebec City, PQ G1K 7P4, Canada
[2] Univ Laval, Fac Pharm, Quebec City, PQ G1K 7P4, Canada
[3] Univ Laval, Fac Med, Dept Pharmacol, Quebec City, PQ G1K 7P4, Canada
[4] Univ Laval, Fac Med, Dept Med Biol, Quebec City, PQ G1K 7P4, Canada
[5] CHUQ, St Francois Assise Hosp, Res Ctr, Quebec City, PQ G1L 3L5, Canada
[6] Univ Laval, Med Res Ctr, CHUQ, Mol Endocrinol Lab, Quebec City, PQ G1V 4G2, Canada
关键词
D O I
10.1016/S0960-894X(99)00262-0
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of novel spermidine and sym-norspermidine dimers was synthesized by crosslinking the polyamine backbones via alkylation of their secondary amino groups to butyl, trans-2-butenyl, 2-butynyl or p-xylyl bridges. The resulting hexamines behaved as high-affinity antagonists of polyamine uptake, with a relative potency that was dependent on the geometry of the linker structure. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1709 / 1714
页数:6
相关论文
共 19 条
[1]  
AZIZ SM, 1995, J PHARMACOL EXP THER, V274, P181
[2]   GENE-TRANSFER WITH SYNTHETIC CATIONIC AMPHIPHILES - PROSPECTS FOR GENE-THERAPY [J].
BEHR, JP .
BIOCONJUGATE CHEMISTRY, 1994, 5 (05) :382-389
[3]   HEXAHYDROPYRIMIDINES AS MASKED SPERMIDINE VECTORS IN DRUG DELIVERY [J].
BERGERON, RJ ;
SELIGSOHN, HW .
BIOORGANIC CHEMISTRY, 1986, 14 (04) :345-355
[4]   DISULFIDES .1. SYNTHESES USING 2,2'-DITHIOBIS(BENZOTHIAZOLE) [J].
BRZEZINSKA, E ;
TERNAY, AL .
JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (26) :8239-8244
[5]  
CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
[6]   TARGETING OF CYTOTOXIC AGENTS BY POLYAMINES - SYNTHESIS OF A CHLORAMBUCIL SPERMIDINE CONJUGATE [J].
COHEN, GM ;
CULLIS, PM ;
HARTLEY, JA ;
MATHER, A ;
SYMONS, MCR ;
WHEELHOUSE, RT .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1992, (04) :298-300
[7]  
COVASSIN L, UNPUB
[8]  
DEMONTIGNY D, UNPUB
[9]  
Duranton B, 1997, CANCER RES, V57, P573
[10]   2,2'-Dithiobis(N-ethyl-spermine-5-carboxamide) is a high affinity, membrane-impermeant antagonist of the mammalian polyamine transport system [J].
Huber, M ;
Pelletier, JG ;
Torossian, K ;
Dionne, P ;
Gamache, I ;
CharestGaudreault, R ;
Audette, M ;
Poulin, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) :27556-27563