Antiviral activity of amides and carboxamides of quinolizidine alkaloid (−)-cytisine against human influenza virus A (H1N1) and parainfluenza virus type 3

Natural Product Research
2021.0

Abstract

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 CC50/IC50 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).

Knowledge Graph

Similar Paper

Antiviral activity of amides and carboxamides of quinolizidine alkaloid (−)-cytisine against human influenza virus A (H1N1) and parainfluenza virus type 3
Natural Product Research 2021.0
Design, synthesis and in vitro anti-influenza A virus evaluation of novel quinazoline derivatives containing S-acetamide and NH-acetamide moieties at C-4
European Journal of Medicinal Chemistry 2020.0
Design, synthesis and anti-influenza A virus activity of novel 2,4-disubstituted quinazoline derivatives
Bioorganic & Medicinal Chemistry Letters 2020.0
Synthesis of Several Cytisine Derivatives and their Cytotoxicities against A431, A375, and HCT 116 Tumor Cell Lines
Chemistry of Natural Compounds 2020.0
Aliphatic and alicyclic camphor imines as effective inhibitors of influenza virus H1N1
European Journal of Medicinal Chemistry 2017.0
Synthesis and antiviral evaluation of cytisine derivatives against dengue virus types 1 and 2
Bioorganic & Medicinal Chemistry Letters 2021.0
(−)-Carbodine: Enantiomeric synthesis and in vitro antiviral activity against various strains of influenza virus including H5N1 (avian influenza) and novel 2009 H1N1 (swine flu)
Bioorganic & Medicinal Chemistry Letters 2010.0
New quaternary ammonium camphor derivatives and their antiviral activity, genotoxic effects and cytotoxicity
Bioorganic & Medicinal Chemistry 2013.0
Identification and Synthesis of Quinolizidines with Anti-Influenza A Virus Activity
ACS Medicinal Chemistry Letters 2014.0
Synthesis and antiviral activity of a series of novel quinoline derivatives as anti-RSV or anti-IAV agents
European Journal of Medicinal Chemistry 2021.0