Growth inhibition of cultured human leukemia cells by 3-aminothymidine and its analogue.
In a previous report, we demonstrated that 3-aminothymidine (1) strongly inhibits the growth of the human T-cell acute lymphoblastoid leukemia cell line CCRF-HSB-2. In order to further study cell growth inhibition by this compound, several of its derivatives and analogues were synthesized and their growth inhibition activities examined using various cultured cell lines. Compound 1 was the most active among the compounds tested and the most effective against cells of the human T-cell acute lymphoblastoid leukemia cell line CCRF-CEM. 3-Methylthymidine (2) also inhibited the growth of CCRF-CEM cells but at a level about one thirtieth that of 1. Introduction of a methyl or acetyl group at the 3-amino group of 1 resulted in the loss of growth inhibition activity. 3-Amino- and 3-methyl-5-bromo-2'-deoxyuridines (6 and 7), the analogues of 1 and 2 both exhibited an ability to inhibit cell growth and their levels of activity were similar in extent, in spite of the difference in their 3-amino and 3-methyl groups, however, these levels were less than that of 1. Compounds 1, 2, 6 and 7 all showed evidence of growth inhibition in every human leukemia cell line examined.
Asano
S
S
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Yokoyama
Y
Y
Kohda
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C091859:3-aminothymidine; D000970:Antineoplastic Agents; D013936:Thymidine