tetano
Editor, Senior Moderator
Eur J Med Chem. 2019 Nov 7:111861. doi: 10.1016/j.ejmech.2019.111861. [Epub ahead of print] [h=1]Design and synthesis of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides as novel dual inhibitors of respiratory syncytial virus and influenza virus A.[/h]
Zhang GN[SUP]1[/SUP], Li Q[SUP]1[/SUP], Zhao J[SUP]1[/SUP], Zhang X[SUP]2[/SUP], Xu Z[SUP]3[/SUP], Wang Y[SUP]1[/SUP], Fu Y[SUP]3[/SUP], Shan Q[SUP]1[/SUP], Zheng Y[SUP]3[/SUP], Wang J[SUP]1[/SUP], Zhu M[SUP]1[/SUP], Li Z[SUP]4[/SUP], Cen S[SUP]5[/SUP], He J[SUP]6[/SUP], Wang Y[SUP]7[/SUP].
[h=3]Author information[/h] 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China; School of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China. 3 College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. 4 School of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China. 5 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. Electronic address: shancen@imb.pumc.edu.cn. 6 College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. Electronic address: jshhe@bjtu.edu.cn. 7 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. Electronic address: wangyucheng@imb.pumc.edu.cn.
[h=3]Abstract[/h] Respiratory syncytial virus (RSV) and influenza A virus (IAV) are two of the most common viruses that cause substantial morbidity and mortality in infants, young children, elderly persons, and immunocompromised individuals worldwide. Currently, there are no licensed vaccines or selective antiviral drugs against RSV infections and most IAV strains become resistant to clinical anti-influenza drug. Here, we described the discovery of a series of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamide as novel and potent RSV and IAV dual inhibitors. Thirty-five derivatives were designed, prepared, and evaluated for their anti-RSV and anti-IAV activities. Among the tested compounds, 14'c, 14'e, 14'f, 14'h, and 14'i exhibited excellent activity against both RSV and IAV, which showed low micromolar to sub-micromolar EC[SUB]50[/SUB] values. Further, compounds 14'c and 14'e were identified as the most promising dual inhibitors with lesser cytotoxicity than the clinical drug, ribavirin. These findings may contribute to the development of a lead compound for the treatment of RSV and/or IAV infections.
Copyright ? 2019 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] 2-((1H-indol-3-yl)thio)-N-Phenyl-acetamide; Dual inhibitors; Influenza A virus; Respiratory syncytial virus
PMID: 31734025 DOI: 10.1016/j.ejmech.2019.111861
Zhang GN[SUP]1[/SUP], Li Q[SUP]1[/SUP], Zhao J[SUP]1[/SUP], Zhang X[SUP]2[/SUP], Xu Z[SUP]3[/SUP], Wang Y[SUP]1[/SUP], Fu Y[SUP]3[/SUP], Shan Q[SUP]1[/SUP], Zheng Y[SUP]3[/SUP], Wang J[SUP]1[/SUP], Zhu M[SUP]1[/SUP], Li Z[SUP]4[/SUP], Cen S[SUP]5[/SUP], He J[SUP]6[/SUP], Wang Y[SUP]7[/SUP].
[h=3]Author information[/h] 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China; School of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China. 3 College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. 4 School of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China. 5 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. Electronic address: shancen@imb.pumc.edu.cn. 6 College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. Electronic address: jshhe@bjtu.edu.cn. 7 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. Electronic address: wangyucheng@imb.pumc.edu.cn.
[h=3]Abstract[/h] Respiratory syncytial virus (RSV) and influenza A virus (IAV) are two of the most common viruses that cause substantial morbidity and mortality in infants, young children, elderly persons, and immunocompromised individuals worldwide. Currently, there are no licensed vaccines or selective antiviral drugs against RSV infections and most IAV strains become resistant to clinical anti-influenza drug. Here, we described the discovery of a series of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamide as novel and potent RSV and IAV dual inhibitors. Thirty-five derivatives were designed, prepared, and evaluated for their anti-RSV and anti-IAV activities. Among the tested compounds, 14'c, 14'e, 14'f, 14'h, and 14'i exhibited excellent activity against both RSV and IAV, which showed low micromolar to sub-micromolar EC[SUB]50[/SUB] values. Further, compounds 14'c and 14'e were identified as the most promising dual inhibitors with lesser cytotoxicity than the clinical drug, ribavirin. These findings may contribute to the development of a lead compound for the treatment of RSV and/or IAV infections.
Copyright ? 2019 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] 2-((1H-indol-3-yl)thio)-N-Phenyl-acetamide; Dual inhibitors; Influenza A virus; Respiratory syncytial virus
PMID: 31734025 DOI: 10.1016/j.ejmech.2019.111861