title: Effect of polyamine homologation on the transport and biological properties of heterocyclic amidines.
abstract: Five sets of heterocyclic derivatives of various sizes and complexities coupled by an amidine function to putrescine, spermidine, or spermine were prepared. They were essentially tested to determine the influence of the polyamine chain on their cellular transport. To comment on affinity and on selective transport via the polyamine transport system (PTS), K(i) values for polyamine uptake were determined in L1210 cells, and the cytotoxicity and accumulation of the conjugates were determined in CHO and polyamine transport-deficient mutant CHO-MG cells, as well as in L1210 and alpha-difluoromethylornithine- (DFMO-) treated L1210 cells. Unlike spermine, putrescine and spermidine were clearly identified as selective motifs that enable cellular entry via the PTS. However, this property was clearly limited by the size of substituents: these polyamines were able to ferry a dihydroquinoline system via the PTS but did not impart any selectivity to bulkier substituents.
authors.affiliation: Groupe de Recherche en Thérapeutique Anticancéreuse, Faculté de Médecine, Université Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes Cedex, France. delcros@univ-rennes1.fr
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Delcros
authors.forename: Sophie
authors.initials: S
authors.lastname: Tomasi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Duhieu
authors.forename: Marine
authors.initials: M
authors.lastname: Foucault
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Martin
authors.forename: Myriam
authors.initials: M
authors.lastname: Le Roch
authors.forename: Vera
authors.initials: V
authors.lastname: Eifler-Lima
authors.forename: Jacques
authors.initials: J
authors.lastname: Renault
authors.forename: Philippe
authors.initials: P
authors.lastname: Uriac
mesh_terms: D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000097:blood / Q000737:chemistry; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D002147:Calmodulin / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003500:Cyclization; D004354:Drug Screening Assays, Antitumor; D000518:Eflornithine / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D015394:Molecular Structure; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000578:Amidines; D002147:Calmodulin; D006146:Guanidines; D011073:Polyamines; D006631:Amine Oxidase (Copper-Containing); C004479:pimagedine; D000518:Eflornithine