Putrescine, Spermidine, Spermine, and Related Polyamine Alkaloids

Publisher Summary This chapter discusses the chemistry, biological, and pharmacological aspects of putrescine, spermidine, spermine, and related polyamine alkaloids. Aliphatic di- and polyamines are widespread in microorganisms, plants, and animals, as conjugates to a number of different biological structures, and also in free form. They are known since; Lewenhoeck examined a linear tetra-amine derivative obtained from sperm, spermine phosphate. In addition to the almost ubiquitous spermine, and the two equally abundant compounds putrescine and spermidine, a great number of other biogenic di-, tri-, and tetra-amine compounds are known. Among these, sym -nor-spermidine, homospermidine, sym-homospennidine, and sym-homospermine are of particular relevance for this treatise because they occur together with putrescine, spermidine, and spermine as fundamental building blocks in polyamine alkaloids. For pharmacological studies, two biological properties of the polyamines and their derivatives are of significance. The first concerns the influence of polyamines on cell proliferation, which makes the polyamines and their derivatives interesting compounds for investigations in the field of neoplastic diseases. The second concerns the interactions of polyamines with ion channels and related receptors, which is interesting with regard to diseases of the central nervous system. With respect to cancer research, the biosynthetic enzymes of polyamines were considered as promising targets for chemotherapy. In particular, spermidine/spermine N 1 -acetyltransferase, the highly regulated key enzyme of polyamine degradation, represents a new target for novel antineoplastic agents. Many synthetic analogs of the natural polyamines have been tested as agents against different cancers, and in some cases the results are rather promising. The interaction of polyamines with ion channels is of central importance for neurotransmittance.