Pharmacological properties biological models

Heparin has been reported to complex with a variety of basic species, including biogenic amines and drugs for reviews, see Refs. 10 and 391. For its possible relevance to the pharmacological properties of heparin and complexed species, mention is made here of complexes with histamine392,393 and anthracycline antibiotics.394 C.d. studies on the interaction of basic homopolypeptides with heparin and other glycosaminogly-cans have shown that heparin is able to induce an ordered, helical conformation in the polypeptide.395 397 Similar, and even more dramatic, effects were observed with mixed basic polypeptides, presumed to represent better models for the biologically relevant interactions with plasma proteins.368... 

The modification of these natural polyhydroxylated compounds via acylation of the hydroxyl functions with aliphatic molecules not only increases their structural diversity, producing analogs that may be useful models for the study of structure-activity relationships, but also changes their physicochemical properties, increasing their solubility in lipophilic media. Moreover, the selective acylation of these natural compounds with various acyl donors could enhance their biological activities, such as their antioxidant and antimicrobial activity, as well as their pharmacological properties [5, 6]. 

Linear as well as cross-linked ionenes are endowed with interesting pharmacological properties. The biological effects of the ionene polymers were investigated and compared with the pharmacological properties of monomeric ammonium salts as well as with existing model compounds [8]. Several systems such as DNA, bacteria, fungi, mammalian cells in culture and laboratory animals were used in these studies. 

Along with these purely pharmacological properties, it is advisable to add other important biological activities that are not directly related to human health, in partictilar the antioxidants used in cosmetics, as well as in weedkillers and insecticides for agricultural use. Padan, an insecticide commonly used in Japan, was prepared by using the model of nereistoxin isolated from the annelid (Polydiaeta) Lumbriconereis heteropoda (see Chapter 21). 

In recent years it has been realized that molecular modeling studies of the alkaloidal molecules having different pharmacological activities are highly important in order to explain their mechanisms, at least partially in some cases. This chapter presents and critically reviews some examples of molecular modeling studies of alkaloids, based on their different biological properties or sometimes performed in parallel to explain their biochemical effects. 

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