Polyamine analogs that activate antizyme frameshifting
Novel polyamines, their synthesis and use in pharmacological, cosmetic or agricultural applications are provided. The polyamines induce antizyme production which in turn down regulates both the production of polyamines by omithine decarboxylase (ODC) and the transport of polyamines by its corresponding polyamine transporter. These compounds will preferably enter the cell independent of the polyamine transporter. As drugs, these compounds are used to treat any disease associated with cellular proliferation including but not limited to cancer.
1. A polyamine having the structure
wherein, n can be 0 to 8 and the aminomethyl functionality can be ortho, meta or para substituted, R is hydrogen, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 7-aminoheptyl, or 8-aminooctyl and R 1 is hydrogen and wherein said polyanilne is non-symmetrical.
2. A polyamine selected from the group consisting of one of the following compounds:
3. A pharmaceutical composition comprising a polyamine according to any one of claims 1 or 2 and a pharmaceutically acceptable excipient, diluent or vehicle.
4. The composition of claim 3 wherein said excipient, diluent or vehicle is pharmaceutically acceptable.
5. The composition of claim 3 wherein said excipient, diluent or vehicle is for topical or intra-aural administration.
6. The composition of claim 3 formulated for intravenous, subcutaneous, intramuscular, intracranial, intraperitoneal, topical, transdermal, intravaginal, intranasal, intrabronchial, intracranial, intraocular, intraaural, rectal, or parenteral administration.
7. The polyamine of claim 1 wherein said structure is
8. The polyamine of claim 1 wherein is
9. The polyarnine of claim 1 wherein said structure is