Current Topics in Medicinal Chemistry - Volume 5, Issue 13, 2005

Recent developments in nucleoside/nucleotide therapeutics and antiviral drug targets are described covering progress in the development of nucleoside/nucleotide mimetics for the treatment of influenza virus, human immunodeficiency virus type 1, hepatitis B and C virus, herpes virus infections; including herpes simplex virus, cytomegalovirus and varicella zoster virus infections, and the highly pathogenic poxviruses (va Read More

Mitochondrial thymidine kinase or TK-2 belongs to the family of mammalian deoxynucleoside kinases (dNKs) that catalyze the phosphorylation of deoxynucleosides to their corresponding deoxynucleoside monophosphates by γ- phosphoryl transfer of ATP. These enzymes are instrumental in the activation of deoxynucleoside analogues with biological and therapeutic properties. Moreover, dNKs are fundamental to maintain dN Read More

MraY presents all necessary biological requirements to be considered as a target of interest for the discovery of novel antibacterials. Furthermore, several inhibitors aimed at this enzyme have been discovered. Amphomycin, which is currently used as a topical antibacterial in the veterinary industry is one of them, but the major source of future developments resides in the nucleoside based inhibitors group. This group has be Read More

Purine nucleoside phosphorylase (PNP), an enzyme involved in the catabolism and recycling of nucleosides, is under investigation for the development of novel antibiotics. One method used for the design of inhibitors is transition state analysis. Chemically stable analogues of a transition state complex are predicted to convert the energy of enzymatic rate acceleration (kcat/knon) into binding energy. Transition st Read More

Escherichia coli purine nucleoside phosphorylase (PNP) catalyzes the cleavage of 9-(2-deoxy-β-Dribofuranosyl)- 6-methylpurine (MeP-dR), while human PNP does not. MeP-dR is well tolerated while the cleavage product, 6-methylpurine (MeP), is highly cytotoxic. This clinical profile suggests an anticancer gene therapy strategy in which solid tumors are transfected with the gene for E. coli PNP. Tumor cells expressing E. coli PNP Read More

Selective agonists and antagonists for A3 adenosine receptors (ARs) are being explored for the treatment of a variety of disorders, including brain and heart ischemic conditions, cancer, and rheumatoid arthritis. This review covers both the structure activity relationships of nucleoside agonist ligands and selected antagonists acting at this receptor and the routes of synthesis. Highly selective agonists have been designed, using Read More