title: Antioxidative properties of natural polyamines and dimethylsilane analogues.
abstract: Structural analogues of natural polyamines, which contain a -Si(CH3)2 group in the central carbon chain, have previously been found to be cytotoxic to various tumor cell lines in vitro and to inhibit tumor cell growth in experimentally grafted animals. In the present study, the antioxidative properties of dimethylsilane polyamine analogues were analyzed in comparison with the natural polyamines. Reactivities of these various polyamines against superoxide anions (generated from the hypoxanthine/xanthine oxidase reaction) and peroxyl radicals (produced from the thermal decomposition of water-soluble 2,2'-azo-bis-[2-amidinopropane] hydrochloride) were investigated. The dimethysilane analogues, and more particularly the hexamine derivative, exhibited the highest scavenging efficiency towards these two reactive oxygen species (ROS). Furthermore, analysis of their ability to prevent hydroxyl radical formation and to trap this ROS showed that the efficiency of the hexamine as a metal chelator and hydroxyl radical scavenger is similar to that of spermine. The higher antioxidant efficiency of the dimethylsilane polyamine analogues with respect to spermidine, together with their ability to displace this polyamine, essential for the promotion of cell growth, from its cellular anionic binding sites that are particularly prone to oxidation, could be biologically relevant and contribute to their in vivo cytotoxic effect and anti-tumor activity. Further experiments will be necessary to demonstrate clearly the relationship between their antioxidant properties and their antiproliferative effects.
authors.affiliation: Inserm U522, CHRU Pontchaillou, Université de Rennes 1, Rennes, France. francois.gaboriau@univ-rennes1.fr
authors.forename: François
authors.initials: F
authors.lastname: Gaboriau
authors.forename: Michel
authors.initials: M
authors.lastname: Vaultier
authors.forename: Jacques-Philippe
authors.initials: JP
authors.lastname: Moulinoux
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Delcros
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors; D008709:Methenamine / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D012016:Reference Values; D012821:Silanes / Q000494:pharmacology*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D011073:Polyamines; D012821:Silanes; C103070:bis(7-amino-4-azaheptyl)dimethylsilane; D013096:Spermine; D017665:Hydroxyl Radical; D008709:Methenamine; D013095:Spermidine