5-(Trifluoromethyl)-beta-l-2'-deoxyuridine, the L-enantiomer of trifluorothymidine: stereospecific synthesis and antiherpetic evaluations.
As a part of our ongoing work on beta-L-nucleoside analogues as potential antiviral drugs, we have synthesized 5-(trifluoromethyl)-beta-L-2'-deoxyuridine (L-TFT), the hitherto unknown L-enantiomer of trifluorothymidine (CF(3)dUrd, TFT). We have also studied the effect of L-TFT on human and herpes simplex virus (HSV) type 1 and 2 thymidine kinases, and human thymidine phosphorylase, as well as its anti-HSV-1 and anti-HSV-2 activities in cell cultures. L-TFT has been found: (i) to inhibit HSV-1 TK with activity comparable to TFT, with no effect on human TK, (ii) to be phosphorylated by the viral enzyme with similar efficiency to TFT, (iii) to be resistant, in contrast to TFT, to hydrolysis by human thymidine phosphorylase. Unfortunately, when evaluated in cell cultures, L-TFT did not show any anti-HSV-1 and anti-HSV-2 activities.
Salvetti
R
R
Dipartimento di Chimica Farmaceutica, Università degli Studi, I-27100 Pavia, Italy.
Marchand
A
A
Pregnolato
M
M
Verri
A
A
Spadari
S
S
Focher
F
F
Briant
M
M
Sommadossi
J P
JP
Mathé
C
C
Gosselin
G
G
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010766:Phosphorylation; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
C434785:5-(Trifluoromethyl)-beta-l-2'-deoxyuridine; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase; D014529:Uridine