| Autor: |
Fedorova VA; Smorodintsev Research Institute of Influenza, Russian Federation, St. Petersburg, Russia., Kadyrova RA; St. Petersburg Pasteur Institute, Russian Federation, St. Petersburg, Russia., Slita AV; St. Petersburg Pasteur Institute, Russian Federation, St. Petersburg, Russia., Muryleva AA; St. Petersburg Pasteur Institute, Russian Federation, St. Petersburg, Russia., Petrova PR; Ufa Institute of Chemistry of UFRC of RAS, Ufa, Russian Federation., Kovalskaya AV; Ufa Institute of Chemistry of UFRC of RAS, Ufa, Russian Federation., Lobov AN; Ufa Institute of Chemistry of UFRC of RAS, Ufa, Russian Federation., Zileeva ZR; Institute of Biochemistry and Genetics of UFRC of RAS, Ufa, Russian Federation., Tsypyshev DO; Bashkir State University, Ufa, Russian Federation., Borisevich SS; Ufa Institute of Chemistry of UFRC of RAS, Ufa, Russian Federation., Tsypysheva IP; Ufa Institute of Chemistry of UFRC of RAS, Ufa, Russian Federation., Vakhitova JV; Institute of Biochemistry and Genetics of UFRC of RAS, Ufa, Russian Federation., Zarubaev VV; St. Petersburg Pasteur Institute, Russian Federation, St. Petersburg, Russia. |
| Abstrakt: |
Novel derivatives of quinolizidine alkaloid ( - )-cytisine were synthesised. ADME properties, cytotoxicity against HEK293 cells and activity against viruses of influenza A/California/07/09(H1N1)pdm09 virus (IAV) and human parainfluenza virus type 3 (HPIV3) were evaluated. It was shown, that 9-carboxamides of methylcytisine (with phenyl and allyl urea's fragments) are most active compounds against IAV probably due to predicted in silico peculiarity of their interactions with the 4R7B active site of IAV neuraminidase. Indexes of selectivity (SI) calculated as ratio of CC 50 /IC 50 of these ureas are 47 and 59 correspondingly. It was also found, that derivatives obtained from allyl isocyanate and ( - )-cytisine or 9,11-dibromocytisine are able to inhibit a reproduction of HPIV3 with SI = 58 and 95. Moreover, last compound - (1 R ,5 R )- N -allyl-9,11-dibromo-8-oxo-1,5,6,8-tetrahydro-2 H -1,5-methanopyrido[1,2- a ][1,5]diazocine-3(4 H )-carboxamide with two bromine atom in 2-pyridone core of starting ( - )-cytisine molecule, demonstrated high activity against HPIV3 (SI = 95) and moderate activity against IAV (SI = 16). |
