title: Camphor-based symmetric diimines as inhibitors of influenza virus reproduction.
abstract: Influenza is a continuing world-wide public health problem that causes significant morbidity and mortality during seasonal epidemics and sporadic pandemics. The purpose of the study was synthesis and investigation of antiviral activity of camphor-based symmetric diimines and diamines. A set of C2-symmetric nitrogen-containing camphor derivatives have been synthesized. The antiviral activity of these compounds was studied against rimantadine- and amantadine-resistant influenza virus A/California/7/09 (H1N1)pdm09 in MDCK cells. The highest efficacy in virus inhibiting was shown for compounds 2a-e with cage moieties bound by aliphatic linkers. The therapeutic index (selectivity index) for 2b exceeded that for reference compounds amantadine, deitiforin and rimantadine almost 10-fold. As shown by structure-activity analysis, the length of the linker has a dramatic effect on the toxicity of compounds. Compound 2e with -C12H24- linker exhibited the lowest toxicity (CTD50=2216μM). Derivatives of camphor, therefore, can be considered as prospective antiinfluenza compounds active against influenza viruses resistant to adamantane-based drugs.
authors.affiliation: Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova St. 2, 630090 Novosibirsk, Russia.
authors.forename: Anastasiya S
authors.initials: AS
authors.lastname: Sokolova
authors.affiliation: Novosibirsk Institute of Organic Chemistry, Siberian Branch of the 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.
authors.forename: O Cyrilliclga I
authors.initials: OC
authors.lastname: Yarovaya
authors.affiliation: Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia.
authors.forename: Dina V
authors.initials: DV
authors.lastname: Korchagina
authors.affiliation: Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia. Electronic address: zarubaev@influenza.spb.ru.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Zarubaev
authors.affiliation: Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Tretiak
authors.affiliation: Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia.
authors.forename: Pavel M
authors.initials: PM
authors.lastname: Anfimov
authors.affiliation: Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia.
authors.forename: Oleg I
authors.initials: OI
authors.lastname: Kiselev
authors.affiliation: Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia.
authors.forename: Nariman F
authors.initials: NF
authors.lastname: Salakhutdinov
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002164:Camphor / Q000737:chemistry*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009980:Influenza A virus / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D007097:Imines; D002164:Camphor
keywords: Antivirals; Camphor; Diimine derivatives; Influenza