The mechanisms of resistance to nucleoside analogues established in preclinical models are rarely found in primary tumors resistant to therapy with these agents. We tested the hypothesis that cells sense sublethal incorporation of analogues into DNA during replication and react by arresting further DNA synthesis and cell cycle progression. After removal of drug, cells may be able to repair dama...

An evaluation of the US Food and Drug Administration's Adverse Event Reporting System identified that patients coinfected with human immunodeficiency virus and chronic hepatitis C virus who were treated with a regimen of ribavirin and didanosine, with or without stavudine, were at increased risk for events associated with mitochondrial toxicity, including fatal hepatic failure, peripheral neuro...

The aim of the thesis was to elucidate the mechanisms underlying resistance to nucleoside analogues used in the treatment of leukemias, with focus on cellular metabolism and induction of apoptosis. Cladribine (CdA), Clofarabine (CAFdA), Fludarabine (Fara-A) and Nelarabine (Ara-G) are nucleoside analogues with activity against various types of leukemias. CAFdA is a relatively new nucleoside anal...

Infectious Diseases Unit, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Received for publication: January 17, 2006. Reprint request: Ubonvan Jongwutiwes, M.D., Infectious Diseases Unit, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. E-mail: [email protected]

a few analogues of atevirdine or 1-[(5-methoxyindol-2-yl) carbonyl]-4-[3- (ethylamino)-2-pyridyl] piperazine – an anti-hiv belonging to non-nucleoside reverse transcriptase inhibitors were synthesized and evaluated for anti-hiv activity. replacement of indolyl moiety with 2-alkylthio-1-benzyl-5-imidazolyl substituent afforded 1-[2-(alkylthio-1-benzyl-5-imidazolyl) carbonyl]-4-[3-(isopropylamino...

There is an extensive list of applications for nucleosides, nucleotides, and their analogues that spans from substrates inhibitors in enzymatic research to anticancer antiviral drugs. Nucleoside phosphates are often obtained by chemical phosphorylation reactions, although nucleoside a promising green alternative. In this work two kinases, D. melanogaster deoxynucleoside kinase B. subtilis deoxy...

This review will describe the recent advances in the synthesis of C-nucleosides with inhibitory activity of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the biosynthesis of guanine nucleotides. The review will cover synthetic approaches of structural analogues showing modifications in the furanose ring as well as in the heterocyclic base. Heterocyclic sugar nucleoside analogues ...

The mechanism of the depletion of ATP, recorded in the erythrocytes of adenosine deaminase-deficient children and of leukemia patients treated with deoxycoformycin, was investigated in normal human erythrocytes treated with this inhibitor of adenosine deaminase. Deoxyadenosine, which accumulates in both clinical conditions, provoked a dose-dependent accumulation of dATP, depletion of ATP, and i...