کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1366298 | 981587 | 2005 | 9 صفحه PDF | دانلود رایگان |

The synthesis and evaluation of 10-methanesulfonyl-DDACTHF (1), 10-methanesulfonyl-5-DACTHF (2), and 10-methylthio-DDACTHF (3) as potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are reported. The compounds 10-methanesulfonyl-DDACTHF (1, Ki = 0.23 μM), 10-methanesulfonyl-5-DACTHF (2, Ki = 0.58 μM), and 10-methylthio-DDACTHF (3, Ki = 0.25 μM) were found to be selective and potent inhibitors of recombinant human GAR Tfase. Of these, 3 exhibited exceptionally potent, purine sensitive growth inhibition activity (3, IC50 = 100 nM) against the CCRF–CEM cell line being 3-fold more potent than Lometrexol and 30-fold more potent than the parent, unsubstituted DDACTHF, whereas 1 and 2 exhibited more modest growth inhibition activity (1, IC50 = 1.0 μM and 2, IC50 = 2.0 μM).
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Journal: Bioorganic & Medicinal Chemistry - Volume 13, Issue 10, 16 May 2005, Pages 3577–3585