Synthesis of Norabietyl and Nordehydroabietyl Imidazolidine-2,4,5-Triones and Their Activity against Tyrosyl-DNA Phosphodiesterase 1
Kseniya S. Kovaleva,
Olga I. Yarovaya,
Irina A. Chernyshova,
Alexandra L. Zakharenko,
Sergey V. Cheresiz,
Amirhossein Azimirad,
Andrey G. Pokrovsky,
Olga I. Lavrik,
Nariman F. Salakhutdinov
Affiliations
Kseniya S. Kovaleva
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, Novosibirsk 630090, Russia
Olga I. Yarovaya
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, Novosibirsk 630090, Russia
Irina A. Chernyshova
Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk 630090, Russia
Alexandra L. Zakharenko
Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk 630090, Russia
Sergey V. Cheresiz
V. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Pirogova St. 1, Novosibirsk 630090, Russia
Amirhossein Azimirad
V. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Pirogova St. 1, Novosibirsk 630090, Russia
Andrey G. Pokrovsky
V. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, Pirogova St. 1, Novosibirsk 630090, Russia
Olga I. Lavrik
Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk 630090, Russia
Nariman F. Salakhutdinov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, Novosibirsk 630090, Russia
New imidazolidine-2,4,5-triones with norabietic, nordehydroabietic, and adamantane substituents were synthesized by reacting oxalyl chloride and the corresponding ureas, providing good yields. Bioisosteric replacement of the ureide group with a parabanic acid fragment made it possible to increase the solubility of compounds and conduct biological studies. The compounds inhibit the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 in submicromolar concentrations. Cytotoxic concentrations were also studied on the glioblastoma cell line SNB19.
