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2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase
Authors:Alexey A. Zeifman  Fedor N. Novikov  Victor S. Stroylov  Oleg V. Stroganov  Ghermes G. Chilov  Alexander Y. Skoblov  Anatoly I. Miroshnikov  Yuri S. Skoblov
Affiliation:1. N.D. Zelinsky Institute Of Organic Chemistry (ZIOC RAS), Leninsky prospekt, 47, 119991 Moscow, Russia;2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia
Abstract:
2,3-Dihydroxy-quinoxaline, a small molecule that promotes ATPase catalytic activity of Herpes Simplex Virus thymidine kinase (HSV-TK), was identified by virtual screening. This compound competitively inhibited HSV-TK catalyzed phosphorylation of acyclovir with Ki = 250 μM (95% CI: 106–405 μM) and dose-dependently increased the rate of the ATP hydrolysis with KM = 112 μM (95% CI: 28–195 μM). The kinetic scheme consistent with this experimental data is proposed.
Keywords:DHQ, 2,3-dihydroxy-quinoxaline   HSV-TK, Herpes Simplex Virus thymidine kinase   TLC, thin layer chromatography
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