title: 2,3-Dihydroxy-quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase.
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.
authors.affiliation: N.D. Zelinsky Institute Of Organic Chemistry (ZIOC RAS), Leninsky prospekt, 47, 119991 Moscow, Russia. Electronic address: azeif@mail.ru.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Zeifman
authors.affiliation: N.D. Zelinsky Institute Of Organic Chemistry (ZIOC RAS), Leninsky prospekt, 47, 119991 Moscow, Russia.
authors.forename: Fedor N
authors.initials: FN
authors.lastname: Novikov
authors.affiliation: N.D. Zelinsky Institute Of Organic Chemistry (ZIOC RAS), Leninsky prospekt, 47, 119991 Moscow, Russia.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Stroylov
authors.affiliation: N.D. Zelinsky Institute Of Organic Chemistry (ZIOC RAS), Leninsky prospekt, 47, 119991 Moscow, Russia.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Stroganov
authors.affiliation: N.D. Zelinsky Institute Of Organic Chemistry (ZIOC RAS), Leninsky prospekt, 47, 119991 Moscow, Russia.
authors.forename: Ghermes G
authors.initials: GG
authors.lastname: Chilov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Skoblov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia.
authors.forename: Anatoly I
authors.initials: AI
authors.lastname: Miroshnikov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia.
authors.forename: Yuri S
authors.initials: YS
authors.lastname: Skoblov
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000251:Adenosine Triphosphatases / Q000737:chemistry*; D002384:Catalysis; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D011810:Quinoxalines; C034983:2,3-dihydroxyquinoxaline; D013937:Thymidine Kinase; D000251:Adenosine Triphosphatases; D000212:Acyclovir
keywords: 2,3-dihydroxy-quinoxaline; DHQ; Enzyme kinetic; HSV-TK; Herpes Simplex Virus thymidine kinase; Inhibition; Molecular docking; TLC; Thymidine kinase; thin layer chromatography