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SHR Neuro Cancer Cardio Lipid Metab Microb
Bretner, M; Schalinski, S; Haag, A; Lang, M; Schmitz, H; Baier, A; Behrens, SE; Kulikowski, T; Borowski, P.
Synthesis and evaluation of ATP-binding site directed potential inhibitors of nucleoside triphosphatases/helicases and polymerases of hepatitis C and other selected Flaviviridae viruses.
Antivir Chem Chemother. 2004; 15(1): 35-42.
Doi: 10.1177/095632020401500104
PubMed
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- Co-authors Med Uni Graz
- Heinze Sarah
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- Abstract:
- 5'-O-(4-fluorosulphonylbenzoyl)-esters of ribavirin (FSBR), adenosine (FSBA), guanosine (FSBG) and inosine (FSBI) were obtained by acylation of the 5'-OH of adenosine, guanosine, inosine, and ribavirin with 4-fluorosulphonylbenzoyl chloride (FSBCI) in HMPA. The above derivatives were tested as inhibitors of nucleoside triphosphatase (NTPase)/helicase activities of Flaviviridae: hepatitis C virus (HCV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and dengue virus (DENV) and polymerase activity of HCV and WNV. When the unwinding activity of viral NTPase/helicases was tested under standard conditions, only weak inhibition was obtained with FSBI (IC50 > or = 120 microM) and in the case of FSBG even an activation was seen. The preincubation of the NTPase/helicases with the 5'-O-FSB derivatives increased the inhibitory effect. Screening of the 5'-O-FSB derivatives on inhibition of the WNV and HCV RNA polymerases employing GTP or UTP substrates revealed rather modest inhibitory effect. FSBI exhibited the highest inhibitory activity against WNV (IC50 = 70 microM with UTP substrate) and HCV polymerase (IC50 = 80 microM with GTP substrate). Other 5'-O-FSB derivatives were very weak inhibitors or completely failed to show any activity against HCV and WNV enzymes. In contrast to the NTPase/helicases the preincubation of the polymerases did not influence the inhibition.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenosine Triphosphate - metabolism
- Binding Sites - administration & dosage
- DNA Helicases - antagonists & inhibitors, metabolism
- DNA-Directed RNA Polymerases - antagonists & inhibitors, metabolism
- Enzyme Inhibitors - chemical synthesis, chemistry, pharmacology
- Esters - chemistry
- Flaviviridae - enzymology
- Hepacivirus - enzymology
- Molecular Structure - administration & dosage
- Nucleoside-Triphosphatase - antagonists & inhibitors, metabolism
- Purine Nucleosides - chemical synthesis, chemistry, pharmacology