Synthesis and antiproliferative effects of novel 5'-fluorinated analogs of 5'-deoxy-5'-(methylthio)adenosine
- 1 May 1989
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 32 (5), 997-1001
- https://doi.org/10.1021/jm00125a012
Abstract
5''-Deoxy-5''-[(monofluoromethyl)thio]adenosine (9) and 5''-deoxy-5''-fluoro-5''-(methylthio)adenosine (10), two novel analogues of 5''-deoxy-5''-(methylthio)adenosine (MTA), have been synthesized and evaluated for their substrate and inhibitory activities toward MTA phosphorylase and for their biological effects in L1210 (MTA phosphorylase deficient) and L5178Y (MTA phosphorylase containing) murine leukemia cell lines. Compound 9 was a potent competitive inhibitor of MTA phosphorylase with a Ki value of 3.3 .mu.M and was also a substrate, with activity approximately 53% that of MTA. Compound 10 was significantly less inhibitory toward the phosphorylase with a Ki value of 141 .mu.M; its lack of substrate activity was attributed to rapid nonenzymatic degradation. The 50% growth inhibitory concentrations (48 h) of 9 were 300 and 200 .mu.M in L1210 and L5178Y cells, respectively; for 10, these respective values were 2 and 0.7 .mu.M. The initial characterization of 9 in these systems reveals that it differs from MTA by not acting as a product regulator of the polyamine biosynthetic pathway.This publication has 12 references indexed in Scilit:
- 5′-Deoxy-5′-methylthioadenosine phosphorylase—IVBiochemical Pharmacology, 1987
- METHYLTHIOADENOSINE PHOSPHORYLASE-DEFICIENCY IN HUMAN LEUKEMIAS AND SOLID TUMORS1986
- COMPARISON OF THE BIOLOGICAL EFFECTS OF 4 IRREVERSIBLE INHIBITORS OF ORNITHINE DECARBOXYLASE IN 2 MURINE LYMPHOCYTIC-LEUKEMIA CELL-LINES1986
- 5′-Deoxy-5′-methylthioadenosine phosphorylase—IIIBiochemical Pharmacology, 1985
- BIOLOGICAL PROPERTIES OF N-4 AND N-1, N-8-SPERMIDINE DERIVATIVES IN CULTURED L1210 LEUKEMIA-CELLS1985
- The comparative effects of 5′-methylthioadenosine and some of its analogs on cells containing, and deficient in, 5′-methylthioadenosine phosphorylaseBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1983
- 5′-Methylthioadenosine metabolism and methionine synthesis in mammalian cells grown in cultureBiochemical and Biophysical Research Communications, 1982
- DEFICIENCY OF METHYLTHIOADENOSINE PHOSPHORYLASE IN HUMAN-LEUKEMIC CELLS INVIVO1982
- 5′-methylthioadenosine phosphorylase—IBiochemical Pharmacology, 1981
- Methylthio group cleavage from methylthioadenosine. Description of an enzyme and its relationship to the methylthio requirement of certain cells in cultureBiochemical and Biophysical Research Communications, 1977