Discovery of a new class of antiviral compounds: camphor imine derivatives.
A new class of compounds featuring a camphor moiety has been discovered that exhibits potent inhibitory activity against influenza A(H1N1)pdm09 and A(H5N1) viruses. The synthesized compounds were characterized by spectroscopic analysis; in addition the structures of compound 2 and 14 were elucidated by the X-ray diffraction technique. Structure-activity relationship studies have been conducted to identify the 1,7,7-trimethylbicyclo[2.2.1]heptanes2-ylidene group as the key functional group responsible for the observed antiviral activity. The most potent antiviral compound is imine 2 with therapeutic index more than 500.
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.
Olga I
OI
Yarovaya
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090, Novosibirsk, Russia.
Andrey V
AV
Shernyukov
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.
Yuriy V
YV
Gatilov
Novosibirsk State University, Pirogova St. 2, 630090, Novosibirsk, Russia.
Yuliya V
YV
Razumova
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
Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376, St. Petersburg, Russia.
Tatiana S
TS
Tretiak
Novosibirsk State University, Pirogova St. 2, 630090, Novosibirsk, Russia.
Andrey G
AG
Pokrovsky
Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376, St. Petersburg, Russia.
Oleg I
OI
Kiselev
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
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002164:Camphor / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D007097:Imines; D002164:Camphor
Antiviral; Cage compounds; Camphor derivatives; Influenza