Aliphatic and alicyclic camphor imines as effective inhibitors of influenza virus H1N1.
A series of camphor derived imines was synthesised and evaluated in vitro for antiviral activity. Theoretical evaluations of ADME properties were also carried out. Most of these compounds exhibited significant activity against the drug-resistant strains of influenza A virus. Especially, compounds 2 (SI = 632) and 3 (SI = 417) presented high inhibition against influenza subtypes A/Puerto Rico/8/34 and A/California/07/09 of H1N1pdm09. Analysis of the structure-activity relationship showed that the activity was strongly dependent on the length of the aliphatic chain: derivatives with a shorter chain possessed higher activity, while the suppressing action of compounds with long aliphatic chains was lower.
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russia.
Anastasiya S
AS
Sokolova
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russia. Electronic address: ooo@nioch.nsc.ru.
Оlga I
ОI
Yarovaya
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia.
Dmitry S
DS
Baev
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia.
Аndrey V
АV
Shernyukov
Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia.
Anna A
AA
Shtro
Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia. Electronic address: zarubaev@influenza.spb.ru.
Vladimir V
VV
Zarubaev
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russia.
Nariman F
NF
Salakhutdinov
D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002164:Camphor / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007097:Imines / Q000737:chemistry*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007097:Imines; D002164:Camphor
Antiviral; Cage compounds; Camphor derivatives; Influenza