[Purine nucleoside phosphorylase inhibitors and their clinical significance].
PNP catalyzes a reversible phosphorolysis of purine deoxy- and ribonucleosides with formation of (d)Rib-1-P and appropriate bases. PNP plays a leading role in the cell metabolism of nucleosides and nucleotides, as well as in maintaining the immune status of an organism. The major purpose of the majority of studies on the PNP is the detection of high-performance enzyme inhibitors, derivatives of the purine nucleosides, which are used in medicine as immunosuppressors. It is well known that the latter are necessary for creating a selective T-cell immunodeficiency in a human body under organs and tissue transplantation. The review discusses the issues related to deliberate synthesis of effective, metabolically inert, and low-toxic PNP inhibitors. It also analyzes the available studies on substrate and inhibitory properties of the analogues of purine nucleosides, as well as research on the structural factors which reinforce the inhibitor activity of those analogues. The inhibitors which are either used in medical practice or are currently at a stage of preclinical testing are described. The inhibitors which are more efficient in their influence on the PNF from tumorous tissues are of special interest. Using PNP inhibitors in case of a number of pathologies denotes the importance and promise of research on both the enzyme and the compounds affecting its activity.
Pogosian
L G
LG
Nersesova
L S
LS
Gazariants
M G
MG
Mkrtchian
Z S
ZS
Meliksetian
G O
GO
Akopian
Zh I
ZhI
D000818:Animals; D015415:Biomarkers / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000172:deficiency / Q000502:physiology; D011687:Purines / Q000378:metabolism; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D015415:Biomarkers; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011687:Purines; D011683:Purine-Nucleoside Phosphorylase