Purine nucleoside analogs

Pharmacology A synthetic purine nucleoside analog, acyclovir has in vitro and in vivo inhibitory activity against HSV-1, HSV-2, and VZV (shingles). 

Chemical Class Acyclic purine nucleoside analog... 

Chemical Class Acyclic purine nucleoside analog ganciclovir derivative I Clinical Pharmacology ... 

Didanosine is a synthetic purine nucleoside analog that inhibits the activity of reverse transcriptase in HIV-1, HIV-2, other retroviruses and zidovudine-resistant strains. A nucleobase carrier helps transport it into the cell where it needs to be phosphorylated by 5 -nucleoiidase and inosine 5 -monophosphate phosphotransferase to didanosine S -monophosphate. Adenylosuccinate synthetase and adenylosuccinate lyase then convert didanosine 5 -monophosphate to dideoxyadenosine S -monophosphate, followed by its conversion to diphosphate by adenylate kinase and phosphoribosyl pyrophosphate synthetase, which is then phosphorylated by creatine kinase and phosphoribosyl pyrophosphate synthetase to dideoxyadenosine S -triphosphate, the active reverse transcriptase inhibitor. Dideoxyadenosine triphosphate inhibits the activity of HIV reverse transcriptase by competing with the natural substrate, deoxyadenosine triphosphate, and its incorporation into viral DNA causes termination of viral DNA chain elongation. It is 10-100-fold less potent than zidovudine in its antiviral activity, but is more active than zidovudine in nondividing and quiescent cells. At clinically relevant doses, it is not toxic to hematopoietic precursor cells or lymphocytes, and the resistance to the drug results from site-directed mutagenesis at codons 65 and 74 of viral reverse transcriptase. 

Cladribine (2-chlorodeoxyadenosine 2-CDA) is a purine nucleoside analog that is resistant to inactivation by adenosine deaminase. The triphosphate form of this agent is incorporated into DNA, resulting in inhibition of DNA synthesis and early chain termination. Cladribine s antitumor activity is unusual for an antimetabolite in that it affects both actively dividing and resting cancer cells. Like fludarabine, cladribine possesses immunosuppressive effects that place patients at risk for serious opportunistic infections. ... 

Ribavirin l-p-D-ribofuranosyl-l/f-l,2,4-triazole-3-carboxamide a purine nucleoside analog that exhibits antiviral activity against a broad spectrum of DNA and RNA viruses. 

Cladribine, a purine nucleoside analog, with antineoplas-tic properties (0.09 mg/kg daily by continuous IV infusion for 7 days), is indicated in the treatment of active hairy cell leukemia. In addition, it has been used in advanced cutaneous T-cell lymphomas, chronic lymphocytic leukemia, non-Hodgkin s lymphomas, acute myeloid leukemias, autoimmune hemolytic anemia, mycosis fungoides, or Sezary syndrome (see also Figure 15). 

LC-separation of low molecular-weight constituents of nucleic acids and intact nucleic acids was reviewed by Zadrazil [358,359], Brown [360] described an enzyme peak shift method verifying peak identities of nucleotides, Singhal [361] reviewed separation and analysis of nucleic acids and their constituents by ion-exclusion and ion exchange column chromatography, and Brown [31,362] summarized the latest developments and state-of-art in HPLC of nucleic acid constituents. Plunkett [363] dealt with the use of HPLC in research of purine nucleoside analogs. 

Didanosine is a purine nucleoside analog active against HlV-1, HIV-2, and HTLV-1. After entering the cell, it is converted by phosphorylation to the active anaboUte dideoxyadenosine 5 -triphosphate. Single codon mutations, including TAMs, can contribute to didanosine resistance. 

Kearney BP, Isaacson E, Sayre J, Ebrahimi R, Cheng AK. The pharmacokinetics of abacavir, a purine nucleoside analog, are not affected by tenofovir DF. Intersci CotfAntimicrob Agents... 

Robak T, Lech-Maranda E, Korycka A, Robak E (2006) Purine nucleoside analogs as immunosuppressive and antineoplastic agents mechanism of action and clinical activity. CurrMed Chem 13 3165-3189... 

J.D. Stoeckler, C.A. Bell, R.E. Parks, Jr., C.K. Chu, J.J. Fox, and M. Ikehara, C(2 )-Substituted purine nucleoside analogs. Interactions with adenosine deaminase and purine nucleoside phosphorylase and formation of analog nucleotides. Biochem. Pharmacol 31 1723 (1982). 

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