Structure-Based Design, Synthesis, and Biological Evaluation of the Cage–Amide Derived Orthopox Virus Replication Inhibitors
Evgenii S. Mozhaitsev,
Evgeniy V. Suslov,
Daria A. Rastrepaeva,
Olga I. Yarovaya,
Sophia S. Borisevich,
Edward M. Khamitov,
Dmitry S. Kolybalov,
Sergey G. Arkhipov,
Nikolai I. Bormotov,
Larisa N. Shishkina,
Olga A. Serova,
Roman V. Brunilin,
Andrey A. Vernigora,
Maxim B. Nawrozkij,
Alexander P. Agafonov,
Rinat A. Maksyutov,
Konstantin P. Volcho,
Nariman F. Salakhutdinov
Affiliations
Evgenii S. Mozhaitsev
Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentyev Ave. 9, 630090 Novosibirsk, Russia
Evgeniy V. Suslov
Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentyev Ave. 9, 630090 Novosibirsk, Russia
Daria A. Rastrepaeva
Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentyev Ave. 9, 630090 Novosibirsk, Russia
Olga I. Yarovaya
Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentyev Ave. 9, 630090 Novosibirsk, Russia
Sophia S. Borisevich
Laboratory of Chemical Physics, Laboratory of Physical and Chemical Methods of Analysis, Ufa Institute of Chemistry Ufa Federal Research Center, 71 Pr. Oktyabrya, 450078 Ufa, Russia
Edward M. Khamitov
Laboratory of Chemical Physics, Laboratory of Physical and Chemical Methods of Analysis, Ufa Institute of Chemistry Ufa Federal Research Center, 71 Pr. Oktyabrya, 450078 Ufa, Russia
Dmitry S. Kolybalov
Synchrotron Radiation Facility SKIF, G.K. Boreskov Institute of Catalysis SB RAS, 630559 Koltsovo, Russia
Sergey G. Arkhipov
Synchrotron Radiation Facility SKIF, G.K. Boreskov Institute of Catalysis SB RAS, 630559 Koltsovo, Russia
Nikolai I. Bormotov
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia
Larisa N. Shishkina
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia
Olga A. Serova
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia
Roman V. Brunilin
Department of Analytical, Physical Chemistry and Polymer Chemistry and Physics, Department of Organic Chemistry, Volgograd State Technical University Lenina, Avenue 28, 400005 Volgograd, Russia
Andrey A. Vernigora
Department of Analytical, Physical Chemistry and Polymer Chemistry and Physics, Department of Organic Chemistry, Volgograd State Technical University Lenina, Avenue 28, 400005 Volgograd, Russia
Maxim B. Nawrozkij
Center of Translational Medicine, Sirius University of Science and Technology, Olympic Avenue 1, Krasnodar Krai, 354340 Sirius, Russia
Alexander P. Agafonov
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia
Rinat A. Maksyutov
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia
Konstantin P. Volcho
Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentyev Ave. 9, 630090 Novosibirsk, Russia
Nariman F. Salakhutdinov
Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentyev Ave. 9, 630090 Novosibirsk, Russia
Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides of benzoic acids containing an adamantane fragment were obtained. Most of the compounds demonstrated activity against vaccinia virus, with a selectivity index SI = 18,214 for the leader compound 18a. The obtained derivatives also demonstrated activity against murine pox (250 ≤ SI ≤ 6071) and cowpox (125 ≤ SI ≤ 3036). A correlation was obtained between the IC50 meanings and the binding energy to the assumed biological target, the p37 viral protein with R2 = 0.60.
