tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2019 Oct 19:126745. doi: 10.1016/j.bmcl.2019.126745. [Epub ahead of print] [h=1]Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents.[/h]
Yarovaya OI[SUP]1[/SUP], Sokolova AS[SUP]2[/SUP], Mainagashev IY[SUP]2[/SUP], Volobueva AS[SUP]3[/SUP], Lantseva K[SUP]3[/SUP], Borisevich SS[SUP]4[/SUP], Shtro AA[SUP]5[/SUP], Zarubaev VV[SUP]3[/SUP], Salakhutdinov NF[SUP]6[/SUP].
[h=3]Author information[/h] 1 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. 2 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia. 3 Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russia. 4 Laboratory of Chemical Physics, Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 71 Octyabrya pr., 450054 Ufa, Russia. 5 Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia. 6 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.
[h=3]Abstract[/h] A chemical library was constructed based on the scaffold of camphecene (2-(E)-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol). The modifications included introduction of mono-and bicyclic heterocyclic moieties in place of the terminal hydroxyl group of camphecene. All compounds were tested for cytotoxicity and anti-viral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells. Among 15 tested compounds 11 demonstrated a selectivity index (SI) higher than 10 and IC[SUB]50[/SUB] values in the micromolar range. The antiviral activity and toxicity were shown to strongly depend on the nature of the heterocyclic substituent. Compounds 2 and 14 demonstrated the highest virus-inhibiting activity with SIs of 106 and 183, and bearing pyrrolidine and piperidine moieties, correspondingly. Compound 14 was shown to interfere with viral reproduction at early stages of the viral life cycle (0-2 h post-infection). Taken together, our data suggest potential of camphecene derivatives in particular and camphor-based imine derivatives in general as effective anti-influenza compounds.
Copyright ? 2019. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Antivirals; Camphecene; Camphor; Imine derivatives; Influenza
PMID: 31668423 DOI: 10.1016/j.bmcl.2019.126745
Yarovaya OI[SUP]1[/SUP], Sokolova AS[SUP]2[/SUP], Mainagashev IY[SUP]2[/SUP], Volobueva AS[SUP]3[/SUP], Lantseva K[SUP]3[/SUP], Borisevich SS[SUP]4[/SUP], Shtro AA[SUP]5[/SUP], Zarubaev VV[SUP]3[/SUP], Salakhutdinov NF[SUP]6[/SUP].
[h=3]Author information[/h] 1 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. 2 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia. 3 Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russia. 4 Laboratory of Chemical Physics, Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 71 Octyabrya pr., 450054 Ufa, Russia. 5 Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia. 6 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.
[h=3]Abstract[/h] A chemical library was constructed based on the scaffold of camphecene (2-(E)-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol). The modifications included introduction of mono-and bicyclic heterocyclic moieties in place of the terminal hydroxyl group of camphecene. All compounds were tested for cytotoxicity and anti-viral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells. Among 15 tested compounds 11 demonstrated a selectivity index (SI) higher than 10 and IC[SUB]50[/SUB] values in the micromolar range. The antiviral activity and toxicity were shown to strongly depend on the nature of the heterocyclic substituent. Compounds 2 and 14 demonstrated the highest virus-inhibiting activity with SIs of 106 and 183, and bearing pyrrolidine and piperidine moieties, correspondingly. Compound 14 was shown to interfere with viral reproduction at early stages of the viral life cycle (0-2 h post-infection). Taken together, our data suggest potential of camphecene derivatives in particular and camphor-based imine derivatives in general as effective anti-influenza compounds.
Copyright ? 2019. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Antivirals; Camphecene; Camphor; Imine derivatives; Influenza
PMID: 31668423 DOI: 10.1016/j.bmcl.2019.126745