tetano
Editor, Senior Moderator
Nat Prod Res. 2019 Dec 2:1-9. doi: 10.1080/14786419.2019.1696791. [Epub ahead of print] [h=1]Antiviral activity of amides and carboxamides of quinolizidine alkaloid (-)-cytisine against human influenza virus A (H1N1) and parainfluenza virus type 3.[/h]
Fedorova VA[SUP]1[/SUP], Kadyrova RA[SUP]2[/SUP], Slita AV[SUP]2[/SUP], Muryleva AA[SUP]2[/SUP], Petrova PR[SUP]3[/SUP], Kovalskaya AV[SUP]3[/SUP], Lobov AN[SUP]3[/SUP], Zileeva ZR[SUP]4[/SUP], Tsypyshev DO[SUP]5[/SUP], Borisevich SS[SUP]3[/SUP], Tsypysheva IP[SUP]3[/SUP], Vakhitova JV[SUP]4[/SUP], Zarubaev VV[SUP]2[/SUP].
[h=3]Author information[/h] 1 Smorodintsev Research Institute of Influenza, Russian Federation, St. Petersburg, Russia. 2 St. Petersburg Pasteur Institute, Russian Federation, St. Petersburg, Russia. 3 Ufa Institute of Chemistry of UFRC of RAS, Ufa, Russian Federation. 4 Institute of Biochemistry and Genetics of UFRC of RAS, Ufa, Russian Federation. 5 Bashkir State University, Ufa, Russian Federation.
[h=3]Abstract[/h] 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[SUB]50[/SUB]/IC[SUB]50[/SUB] 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,5R)-N-allyl-9,11-dibromo-8-oxo-1,5,6,8-tetrahydro-2H-1,5-methanopyrido[1,2-a][1,5]diazocine-3(4H)-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).
[h=4]KEYWORDS:[/h] (−)-Cytisine; ADME; HEK293; influenza virus; molecular docking; parainfluenza virus; ureas
PMID: 31790286 DOI: 10.1080/14786419.2019.1696791
Fedorova VA[SUP]1[/SUP], Kadyrova RA[SUP]2[/SUP], Slita AV[SUP]2[/SUP], Muryleva AA[SUP]2[/SUP], Petrova PR[SUP]3[/SUP], Kovalskaya AV[SUP]3[/SUP], Lobov AN[SUP]3[/SUP], Zileeva ZR[SUP]4[/SUP], Tsypyshev DO[SUP]5[/SUP], Borisevich SS[SUP]3[/SUP], Tsypysheva IP[SUP]3[/SUP], Vakhitova JV[SUP]4[/SUP], Zarubaev VV[SUP]2[/SUP].
[h=3]Author information[/h] 1 Smorodintsev Research Institute of Influenza, Russian Federation, St. Petersburg, Russia. 2 St. Petersburg Pasteur Institute, Russian Federation, St. Petersburg, Russia. 3 Ufa Institute of Chemistry of UFRC of RAS, Ufa, Russian Federation. 4 Institute of Biochemistry and Genetics of UFRC of RAS, Ufa, Russian Federation. 5 Bashkir State University, Ufa, Russian Federation.
[h=3]Abstract[/h] 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[SUB]50[/SUB]/IC[SUB]50[/SUB] 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,5R)-N-allyl-9,11-dibromo-8-oxo-1,5,6,8-tetrahydro-2H-1,5-methanopyrido[1,2-a][1,5]diazocine-3(4H)-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).
[h=4]KEYWORDS:[/h] (−)-Cytisine; ADME; HEK293; influenza virus; molecular docking; parainfluenza virus; ureas
PMID: 31790286 DOI: 10.1080/14786419.2019.1696791