Iodine antiviral activity

The antiviral activity of 322, determined351 using primary rabbit kidney cells injected with HS V-l (Herpes Simplex Virus type 1), showed that BVFRU has antiviral potency and transport characteristics suitable for in vivo diagnosis of HSE (Herpes Simplex Encephal-ities) because of greater stability of bromine-carbon bonds than iodine-carbon bond present in [131I]IVDU352, [( )-5-(2-iodovinyl)-l-(2-deoxy- -D-ribofuranosyl)uracil]. 

Despite the multitude of functional groups present and the insolubility of the nucleosides in inert solvents, palladium-catalyzed coupling reactions have been used in their synthesis. Thus, the coupling of terminal alkynes with iodinated uracyl nucleosides proceeds in high yield in the presence of a Pd°-Cu catalyst in warm triethylamine, and several of the products obtained by this route have shown useful antiviral activity (Scheme... 

Other halogenated uridine derivatives have been reported to exhibit antiviral activity. Fluorodeoxyuridine has in vitro antiviral activity but is not used in clinical practice. Bromodeoxyuridine is used in subacute sclerosing panencephalitis, a deadly, virus-induced CNS disease. This agent appears to interfere with DNA synthesis in the same way as idoxuridine. The 5 -amino analogue of idoxuridine (5-iodo-5 -amino-2, 5 -dideoxyuridine) is a better antiviral agent than idoxuridine, and it is less toxic. It is metabolized in herpesvirus-infected cells only by thymidine kinase to di- and triphosphoramidates. These metabolites inhibit HSV-specific late RNA transcription, causing reduction of less infective abnormal viral proteins. 5-Bromo-2 -deoxyuridine has an action similar to that of other iodinated compounds. None of these compounds are commercially available in the United States. 

Iodine is known for its broad spectrum of antimicrobial and antiviral activity it kills aU known microflora. The need to unveil the details of the interaction of iodine complexes with biomolecules has grown considerably in recent years. On the one hand, this is due to the search for the interrelationship between the characteristics of donor-acceptor complexes and physiological and biological activity of their constituent molecules. On the other hand, it is because of successful developments of a number of biologically active compounds and drugs containing iodine complexes. 

Pharmaceutical compounds containing complexes of molecular iodine have a wide spectrum of antibacterial and antiviral activity, including HIV. However, all known iodine-containing drags are characterized as highly toxic substances and therefore in fact are not used in medical practice for parenteral application. 

The 5-phosphates of several antiviral acyclonucleosides (50) have been prepared in yields between 60 and 65% by reaction of the corresponding iodo derivatives with trisodium thiophosphate in water. The iodo derivatives were synthesised from the parent acyclonucleosides by initial formation of the N, 0-bis acetyl derivatives (51) by reaction with triethylorthoformate followed by acid hydrolysis of the cyclic orthoester intermediate and then iodination with iodine/ trphenylphosphine/ imidazole. None of the derivatives were active against HSV-1, HSV-2 or CMV. 

Various biological activities such as antimicrobial [111-113], antiviral [114], antidepressant [115], analgesic, and anti-inflammatory [116] have been recently reported for thienopyrimidine compounds. Mehdi et al. [117] developed a new iodine-catalyzed route for the synthesis of thieno[2,3-( pyrimidine derivatives 75 via heterocyclization of 2-amino-4,5-dimethylthiophene-3-carboxamide 74 with aromatic aldehydes (Scheme 10.55). 

An ideal antimicrobial agent should be non-toxic and possess broad-spectrum antiviral, antibacterial, and antifungal activity and exclude resistance. This has led to the design of a combination agent, iodine-lithium-alpha-dextran [66 ]. This uses the non-specific antimicrobial action of molecular and ionized iodine and the systemic immunomodulatory effects of the polysaccharide complex of iodine and lithium. This new agent has been assessed by parenteral administration in HIV-infected patients. The adverse effects of phlebitis of punctured small veins and subfebrile fever,... 

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