Adenine arabinoside ara

Vidarabine (adenine arabinoside, ara-A) is phos-phorylated in the cell to the triphosphate derivative which blocks DNA synthesis by inhibiting DNA polymerase. It is indicated for infections with herpes simplex virus and varicella-zoster however its use has to a large extend been surpassed by aciclovir. It is administered topically or intravenously. It is inactivated rapidly by adenosine deaminase which for systemic use necessitates constant infusion of the drug. Vidarabine is the least toxic of the purine analogues. Nausea and vomiting are the most frequent adverse effects and neurotoxicity may occur. 

Vibramycin doxycycline. vidarabine [ban. inn. jan. usan) (adenine arabinoside Ara-A Vira-A ) is a purine nucleoside ANTIVIRAL isolated from the marine gorgonian Evnicella cavoUni and Streptomyces spp. Clinically, it may be used to treat herpes simplex and vaccinia infections. 

Synonyms adenine arabinoside ara-A Trade names Arasena Vira-A Ophthalmic (Pfizer) Indications Herpetic keratoconjunctivitis Category Antiviral, nucleoside analog Half-life 3.3 hours... 

Corticosteroids. Corticosteroids are immunosuppressant drugs which have had beneficial effects in autoimmune chronic active hepatitis. They were investigated for the treatment of ehronic aetive hepatitis B (183-185), resulting in increased HBV replication, membrane expression of viral antigen, and delayed HBeAg seroconversion (132, 186). Stopping steroid treatment usually leads to a rebound in hepatic disease activity but may be followed by termination of viral replication within a few months (187). Thus, despite the decrease in transaminase activity, corticosteroids have little role in the treatment of chronic hepatitis B. However, corticosteroids may be useful for pretreatment of certain patients prior to interferon therapy (188) or for enhaneing the efficacy of interferon or adenine arabinoside (ARA-A) treatment by prior steroid withdrawal in patients with mild inflammatory activity (189). 

The human dream of finding an antiviral antibiotic from microbial origin which selectively affects the viral but not the host cell in a similar manner to the regular antibiotics has not become a reality. However, several microbial-derived metabolites show promising activity. The use of microbes to modify synthetic compounds or to accomplish specific desired reaction is common in pharmaceutical industry. Adenine arabinoside (Ara A, 200), which is approved for clinical investigation, is also produced by a Streptomyces sp [19]. Examples of secondary... 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Vidarabine is an adenine arabinoside which shows in vitro activity against HSV, VZV and CMV. It is phosphorylated intracellularly by host enzymes to form ara-ATP which inhibits viral DNA polymerase. It is incorporated into both viral and cellular DNA and shows some animal teratogenicity [13],... 

Perhaps best known of the nucleoside analogues are the arabinose compounds Ara(C) (cytosine arabinoside, l-jS-D-arabinofuranosylcytosine) and Ara(A) (adenine arabinoside, 9-j8-D-arabinofuranosyladenine). Both compounds are triphosphorylated [converted to Ara(CTP) and Ara(ATP) in vivol upon which they may exert a dual action on DNA polymerase. They may inhibit DNA polymerase (for example, Ara(CTP) inhibits DNA polymerase II and III) and they may be incorporated into newly synthesized DNA. In fact, Ara(C) but not Ara(A) is also incorporated into RNA. Such uptake into DNA is lethal since a subtle difference will develop in the DNA geometry as a result of the cytosine base adapting a new glycosidic bond angle due to steric hindrance from the 2 -hydroxyl function. 

In an assessment of the vitro susceptibility of HSV to antiviral drugs, utilizing a plaque reduction assaya rabbit kidney cell culture system produced lower MIC s than did a hamster kidney cell system. Of the two types of HSV tested (types I and II, a total of 21 strains), both exhibited an vitro spectrum for susceptibility to IHDR, which may account for some of the differences previously reported. HSV-I was most consistently inhibited by lUDR and Ara-C, while Ara-C was most effective against HSV-II. Adenine arablnoside (Ara-A) and hypoxanthine-arabinoside were less effective against both HSV types. 

Numerous syntheses have also been reported for arabinofuranosyl nucleoside analogues, prepared either conventionally from arabinofuranosyl derivatives or via 2,2-anhydro-nucleosides obtained from appropriate ribonucleosides. 5-Aza-cytosine-D-arabinoside has been synthesized and found to show similar antiviral activity to Ara-C(arabinosyl-cytosine). 7-a-, 7-<3-, 9-0 -, and 9- 3-arabino-furanosyl derivatives of 3-deazaguanine have also been prepared, but none showed any anti-tumour activity. 9-(o -D-Arabinofuranosyl)-8-aza[2- C]-adenine, 7-(/3-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine-4(3//)-one (15)," l-(a-D-arabinofuranosyl)- and l-(/3-D-xylofuranosyl)-4-nitropyrazole, and Ot-arabino-nucleosides of 5-fluoro-cytosine and -uracil derivatives have also been prepared. An improved synthesis of 9-(/3-D-arabinofuranosyl)-2-fluoro-adenine has been reported. The ratio of o to 3 anomers obtained by phase-transfer reaction of 2,3,5-tri-O-benzyl-D-arabinofuranosyl bromide with 6-chloro-2-thiomethyl-7-deazapurine varied with the quaternary ammonium salt used as a catalyst, although the jU-anomer predominated in every case. 2,2-Anhydro-nucleosides have been used to prepare l-j3-D-arabinofiiranosyl derivatives of 5-alkylthio-uracils, 5-ethyl-cytosine, and 5-ethyl-uracil, 8-alkylamino-purines, and 2-aralkylamino-l,4-dihydro-4-imino-pyrimidine hydrochlorides (16). ... 

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