Polyamines cytotoxic

So far the most potent anti-HIV compounds in vitro among the macro-cyclic polyamines are dinuclear zinc(II) complex of m-xylyl-biscyclen (23) (by Kimura s group) and p-xylyl-biscyclam (30) (by De Clercq s group). They are active against various strains of HIV-1 and HIV-2, while cytotoxicity towards host MT-4 cells are minimal. Their activity against HIV is selective and they are not active against other viruses tested. Hence, the study of their mode of action is not only useful in developing... 

Other investigators have considered polyamines as polymeric drugs. Panarin and coworkers [467] studied the immunogenic and antibacterical activity of water-soluble cationic polyelectrolytes based on vinylamine amino-alkyl methacrylate quaternary ammonium salts. Macrophages were successfully activated in vivo to become cytotoxic to tumor cells in vitro, and cytotoxic or... 

Other cationic lipids combine several elements of different families, for example DOSPA, which is composed of a quaternary ammonium salt and polyamine spermine. The formulation of DOSPA with DOPE results in the well-known commercial Lipofectamine (Hawley-Nelson et al., 1993). Although this lipid displayed high transfection activity, its cytotoxicity prevented its further development. 

Three families of polymers have been used to study transfection mechanisms polyamines, polyamides, and polyvinyl type polymers. The transfection efficiencies achievable with these systems vary widely, so an in-depth analysis of each polymer family and subsequent comparison of what affects gene delivery will be discussed in this chapter. In addition to high transfection efficiency, it is important for the polymeric systems to be relatively nontoxic to cells in vitro and not to elicit an immune response in vivo. Thus, the effect of transfection parameters on cytotoxicity and immunogenicity will also be examined. 

This review deals with the syntheses of various hyperbranched polyamines that are prepared through a one-step polymerization process. Furthermore, we present the current status of polyamines as gene carriers and describe their versatility, and their properties such as structure-property dependency, gene transfection efficiency, and cytotoxicity profiles of hyperbranched polyamines. 

Keywords Applications Cytotoxicity profile Gene delivery Hyperbranched polyamines Poly(amido amine) Poly(amido ester) Poly(ethylene imine) Polyglycerol amines Structure-property dependence Synthesis Transfection efficiency... 

Cells treated with 5-FU undergo cell cycle arrest or apoptosis by inhibition of DNA synthesis. When human oral squamous cell carcinomas (HSC-2, HSC-3, HSC-4) were treated with 5-FU, viable cell numbers declined dose-dependently (CC50 determined after 24 hours treatment 3.4,6.9 and 1.7 p,M, respectively). The intracellular putrescine concentration slightly declined (Table 2) [29]. The combination treatment of 5-FU with N(l),N(ll)-diethylnorspermine (DEN-SPM), which is an inducer of spermidine/spermine N(l)-acetyltransferase (SSAT) that depletes polyamine, has been reported to augment the cytotoxic activity of 5-FU, suggesting possible clinical application [30]. 

Table 4 Cytotoxicity and antitumor activity of platinum polyamine complexes in murine leukemia sensitive (L1210) and resistant to CDDP (L1210/CDDP) and in the LX-1 human tumor xenografP...

Polyamines, such as spermine, spermidine, putrescine, cadaverine, are natural substances widely distributed in vegetable, animal and bacterial cells. They enter in the composition of bacterial viruses. They have a wide range of effects, but they are difficult to localize within the cell and their physiological significance is not understood very well. In animal cells and sera there exists a diamineoxidase which converts spermine into highly cytotoxic compounds, and many effects seen in tissue cultures are attributed to these substances. 

Seiler N (2005) Pharmacological aspects of cytotoxic polyamine analogs and derivatives for cancer therapy. Pharmacol Ther 107 99-119... 

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