Tropolone and its derivatives as inhibitors of the helicase activity of hepatitis C virus nucleotide triphosphatase/helicase.
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Tropolone and its derivatives as inhibitors of the helicase activity of hepatitis C virus nucleotide triphosphatase/helicase. / Borowski, Peter; Lang, Melanie; Haag, Annemarie; Baier, Andrea.
in: ANTIVIR CHEM CHEMOTH, Jahrgang 18, Nr. 2, 2, 2007, S. 103-109.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Tropolone and its derivatives as inhibitors of the helicase activity of hepatitis C virus nucleotide triphosphatase/helicase.
AU - Borowski, Peter
AU - Lang, Melanie
AU - Haag, Annemarie
AU - Baier, Andrea
PY - 2007
Y1 - 2007
N2 - In this report, we demonstrate the interaction of the non-structural protein 3 (NS3) of hepatitis C virus (HCV) with alkaloide tropolone (2-hydroxy-2,4,6-heptatriene-1-one) and its derivatives. The compounds were biochemically screened separately against the ATPase and helicase activities of HCV NS3. In the investigations presented, alkaIoide tropolone and its derivatives significantly inhibited the helicase activity of the viral protein when using a DNA substrate, with 50% inhibitory concentration values within a low micromolar range. The results using the RNA substrate were unexpected--none of the tropolone derivatives excerted any modulating influence towards the unwinding activity. Surprisingly, no influence of the nucleoside triphosphatase (NTPase) turnover was observed. Evidence is presented confirming that these compounds do not act by blocking the NTP-binding site, but by occupying an additional allosteric regulatory site. Further mechanisms of action, particularly of some of the derivatives, are discussed.
AB - In this report, we demonstrate the interaction of the non-structural protein 3 (NS3) of hepatitis C virus (HCV) with alkaloide tropolone (2-hydroxy-2,4,6-heptatriene-1-one) and its derivatives. The compounds were biochemically screened separately against the ATPase and helicase activities of HCV NS3. In the investigations presented, alkaIoide tropolone and its derivatives significantly inhibited the helicase activity of the viral protein when using a DNA substrate, with 50% inhibitory concentration values within a low micromolar range. The results using the RNA substrate were unexpected--none of the tropolone derivatives excerted any modulating influence towards the unwinding activity. Surprisingly, no influence of the nucleoside triphosphatase (NTPase) turnover was observed. Evidence is presented confirming that these compounds do not act by blocking the NTP-binding site, but by occupying an additional allosteric regulatory site. Further mechanisms of action, particularly of some of the derivatives, are discussed.
M3 - SCORING: Zeitschriftenaufsatz
VL - 18
SP - 103
EP - 109
JO - ANTIVIR CHEM CHEMOTH
JF - ANTIVIR CHEM CHEMOTH
SN - 0956-3202
IS - 2
M1 - 2
ER -
