Inhibitors of purine nucleoside phosphorylase: Effects of 9-deazapurine ribonucleosides and synthesis of 5‘-deoxy-5’-iodo-9-deazainosine Journal Article
| Authors: | Stoeckler, J. D.; Ryden, J. B.; Parks, R. E. Jr; Chu, M. Y.; Lim, M. I.; Ren, W. Y.; Klein, R. S. |
| Article Title: | Inhibitors of purine nucleoside phosphorylase: Effects of 9-deazapurine ribonucleosides and synthesis of 5‘-deoxy-5’-iodo-9-deazainosine |
| Abstract: | 9-Deazapurine ribonucleosides constitute a new class of noncleavable purine nucleoside phosphorylase inhibitors that have at least 30-fold greater affinity for the enzyme than the corresponding C-nucleosides of the formycin B series. 9-Deazaguanosine, 9-deazainosine, and 5‘-deoxy-5’-iodo-9-deazainosine competitively inhibited human erythrocytic purine nucleoside phosphorylase with K1 values of 29, 20, and 1.8 x 10-7 M. The last compound is the most potent nucleoside inhibitor of the enzyme presently available and its synthesis is described. In contrast, 7,9-dideaza-7-thiainosine is a very weak inhibitor of the enzyme. When tested as an inhibitor of 2’–deoxyguanosine phosphorolysis in intact human erythrocytes and MOLT-3 human T-cell lymphoblastic leukemia cells, ‘-deoxy-5’ was equipotent with 8-aminoguanosine (which is a precursor for 8-aminoguanine, K1 = 2 x I0-7m).Similarly, 5‘-deoxy-5’-iodo-9-deazainosine and 8-aminoguanosine both potentiated the growth inhibition of human T-lymphocytic MOLT-3 cells by 2’–deoxyguanosine, reducing the 50% inhibitory concentration from -2 x 10-5 to -2 x 10–6M. © 1986, American Association for Cancer Research. All rights reserved. |
| Keywords: | unclassified drug; human cell; dose response; drug potentiation; enzyme inhibition; cell line; in vitro study; drug screening; drug synthesis; structure-activity relationship; lymphatic system; guanine; guanosine; drug response; deoxyguanosine; erythrocyte; drug cytotoxicity; lymphatic leukemia; radioisotope; synthesis; normal human; erythrocytes; growth inhibition; pentosyltransferases; purine-nucleoside phosphorylase; intoxication; drug comparison; purine nucleoside phosphorylase; leukemia, lymphocytic; purine nucleosides; inosine; humans; human; priority journal; article; t lymphoblast; blood and hemopoietic system; 5' deoxy 5' iodo 9 deazainosine; 8 aminoguanosine; 9 deazaguanosine; 9 deazainosine; deoxyguanosine c 14; thieno[3,2 d]pyrimidin 4(3h) one 7 riboside; cell strain molt 3; formycins |
| Journal Title: | Cancer Research |
| Volume: | 46 |
| Issue: | 4 Pt. 1 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1986-04-01 |
| Start Page: | 1774 |
| End Page: | 1778 |
| Language: | English |
| PUBMED: | 3081256 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 18 August 2021 -- Source: Scopus |
