Polymers antiviral activity

Since the pioneer work by Merigan in 1967 [1], many kinds of synthetic or natural polyanionic polymers have been examined for their biological activities [2-8], such as cytotoxicity, antiviral activity, antitumor activity, and immunomodulating activity. Although the biological results were interesting, the extent of activity for clinical application was still low. 

Anionic polyelectrolytes have been shown to enhance resistance to bacteria and fungi, enhance immune response, inhibit adjuvent arthritis and either depress or stimulate phagocytic activity of the reticuloendothelial system [458,459]. Carboxylic acid polymers have shown interferon induction, antiviral activity, and tumor growth inhibition [460]. The effects include inhibition of sarcoma, leukemia, polyoma and vesicular stomatitis virus. In one application, the cytotoxicity of bleomycin toward cultured mammalian cells was synergisti-cally enhanced by stirring in the presence of high molecular weight polyfacrylic acid) [461]. 

Pitha and co-wodcers (43) have been able to demonstrate in a series of studies the poly(vinyl uracil) [10] and polyfvinyladenin) [22] to show in fact antiviral activity, but probably no interferon induction. Rather, it has been shown, that these electrically neutral polymers with a molecular weight... 

A review article on synthetic polymers with antiviral activity and their clinical application has been published by Tarasov et al. (51). 

Antibacterial, antihelmintic, antiviral activity, anaesthetic, inflammatory [327], analgetic [328], inhibitors of phenylethanolamine IV-methyltransferase in pharmaceutical composition [329], high electroconductivity [330], in manufacture of epoxy polymers [331], in photography [332-335], metal corrosion inhibition [336-338]... 

P. C.de S. F. Tischer, L. B. Talarico, M. D. Noseda, S. M. P. B. Guimaraes, E. B. Damonte, and M. E. R. Duarte, Chemical structure and antiviral activity of carrageenans from Meristiella gelidium against herpes simplex and dengue virus, Carbohydr. Polym., 63 (2006) 459 165. 

Removal of the polymer from the site of its antiviral activity to an insulated site is an interesting and unusual process, leading to a loss of beneficial drug effects. Small molecular weight drugs are excreted of metabolically transformed into inactive compounds a polymer that cannot be excreted or degraded is converted into in itive form by autophagy. 

A second structural feature for interferon induction by polycarboxylates is the presence of negative charges. They may be placed in either alternate (PAA) or adjacent (pyran copolymer) position but should occur in a regular and dense sequence. The polyanionic character of the polymer appears to be a prerequisite for interferon induction, antiviral activity and antibacterial activity, since uncharged polymers such as dextran, polyacrylamide, non-carboxylated polyethylene analogues of pyran copolymers and incompletely oxidized amylose were devoid of any of these activities48,49,51,107). 

More recently, in the 1980s and 1990s new series of fused phenothiazine derivatives, the benzo[a,b or c]phenothiazines (BPHTs), were synthesized [3, 21 and references therein] and have received a great deal of attention, mainly because of their potential applications and their important biomedical properties [12-24]. Indeed, some BPHTs are coloured compounds and have been applied as polycyclic dyes or pigments for synthetic polymers, and also in optical recording media ([21] and references therein). Moreover, certain benzo [a or c]phenothiazine derivatives are potential anti-helmintics, possess an antiviral activity, for example inhibiting the multiplication of encephalomyocarditis viruses in tissue cultures ([21,22], and refer-... 

Takemoto and coworkers have prepared a wide variety of monomeric derivatives of a number of nucleic acid bases in order to prepare simple analogs of RNA and DNA (23.24). Some of these synthetic polymers do show base-base interactions that are similar to those observed in natural DNA and RNA materials. Pltha has observed anticancer and antiviral activity for some vinyl derivative polymers of uracil or adenine (25). 

Antitumor and Antiviral Activity of Polycarhoxyllc Acid Polymers... 

The polymer structure had a more significant effect on antiviral activity (Table II). Pyran and PAAMA produced approximately the same activity while PMA and BCEP were very poor. Further, molecular weight had a dramatic effect. The lower molecular weight fractions (<30,000) were ineffective and only the higher molecular weight materials (>30,000) were active. 

Consequently, we are observing two significant effects with regard to antitumor and antiviral activity. These effects appear to be related in most cases, to the polymer structure and molecular weight. 

Amino derivatives of the ring system have been patented as pharmaceuticals, and 2,3-dioxo compounds are claimed to have antiviral activity. A large series of pyrazino[2,3-h]pyrazines have been described as provoking ataxia by lowering CNS activity. More complex derivatives have found use in the formation of polymers. Perhydro derivatives are useful in the preparation of dyes and pharmaceuticals and in accelerating vulcanization. ... 

Biological Tests The polymers were tested as single. strands in eukaryotic and viral polymerase systems In base-paired complexes with their mate polynucleotides they were tested with regard to antiviral activities in establishing antiviral states, inducing and priming interferon. 

A number of platinum polyamines were tested for antiviral activity in tumor cells [111]. For instance, the polymer from tetrachloroplatinate and 2,6-diamino-3-nitroso-pyridine (Scheme 8.34) which exhibited a cell differential ratio of 3.4, was tested at a concentration of 2.2 Xg/ml on L929 cells infected with... 

We have been involved in the synthesis and characterization of organotin polymers for over 30 years. The synthesis of organotin polymers was recently reviewed [2]. Much of our interest in organotin polymers is related to their antibacterial, anticancer, and antiviral activity [2-32], The antibacterial and anticancer activity of these polymers has been recently reviewed [2,3]. 

Lee, K.J. et al., Soluble-polymer supported synthesis of a prostanoid library identification of antiviral activity, Org. Lett., 1, 1859, 1999. 

TABLE II Antitumor and Antiviral Activity With Polymer Molecular Weight. 

These studies suggest that (a) the biological toxicity of polyanions increases with molecular weight (significant toxicity increases occur above 15,000 MW and becomes serious over 50,000 MW) (b) antitumor activity does not appear to be molecular weight dependent (c) antiviral activity is related to molecular weight (it is diminished below 50,000 MW) and (d) sensitization to bacterial endotoxin is related to molecular weight in the case of pyran and seems to be affected by polydispersity of the polyanionic polymer. 

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