tetano
Editor, Senior Moderator
Eur J Med Chem
. 2021 Aug 13;225:113762.
doi: 10.1016/j.ejmech.2021.113762. Online ahead of print.
Discovery of novel thiophene derivatives as potent neuraminidase inhibitors
Zhi Jian Zhong[SUP] 1 [/SUP], Xiao Tong Hu[SUP] 2 [/SUP], Li Ping Cheng[SUP] 3 [/SUP], Xing Yong Zhang[SUP] 1 [/SUP], Qiang Zhang[SUP] 4 [/SUP], Ju Zhang[SUP] 5 [/SUP]
Affiliations
Abstract
Neuraminidase (NA) is an important target for the treatment of influenza. In this study, a new lead NA inhibitor, 4 (ZINC01121127), was discovered by pharmacophore-based virtual screening and molecular dynamic (MD) simulation. Some novel NA inhibitors containing thiophene ring were synthesized by optimizing the skeleton of the lead compound 4. Compound 4b had the most potent inhibitory activity against NA (IC[SUB]50[/SUB] = 0.03 μM), which was better than the positive control oseltamivir carboxylate (IC[SUB]50[/SUB] = 0.06 μM). 4b (EC[SUB]50[/SUB] = 1.59 μM) also exhibits excellent antiviral activity against A/chicken/Hubei/327/2004 (H5N1-DW), which is superior to the reference drug OSC (EC[SUB]50[/SUB] = 5.97 μM). Molecular docking study shows that the thiophene moiety plays an essential role in compound 4b, which can bind well to the active site of NA. The good activity of 4b may be also ascribed to the extending of quinoline ring into the 150-cavity. The results of this study may provide an insightful help for the development of new NA inhibitors.
Keywords: 150-Cavity; Neuraminidase inhibitor; Thiophene; Virtual screening.
. 2021 Aug 13;225:113762.
doi: 10.1016/j.ejmech.2021.113762. Online ahead of print.
Discovery of novel thiophene derivatives as potent neuraminidase inhibitors
Zhi Jian Zhong[SUP] 1 [/SUP], Xiao Tong Hu[SUP] 2 [/SUP], Li Ping Cheng[SUP] 3 [/SUP], Xing Yong Zhang[SUP] 1 [/SUP], Qiang Zhang[SUP] 4 [/SUP], Ju Zhang[SUP] 5 [/SUP]
Affiliations
- PMID: 34411893
- DOI: 10.1016/j.ejmech.2021.113762
Abstract
Neuraminidase (NA) is an important target for the treatment of influenza. In this study, a new lead NA inhibitor, 4 (ZINC01121127), was discovered by pharmacophore-based virtual screening and molecular dynamic (MD) simulation. Some novel NA inhibitors containing thiophene ring were synthesized by optimizing the skeleton of the lead compound 4. Compound 4b had the most potent inhibitory activity against NA (IC[SUB]50[/SUB] = 0.03 μM), which was better than the positive control oseltamivir carboxylate (IC[SUB]50[/SUB] = 0.06 μM). 4b (EC[SUB]50[/SUB] = 1.59 μM) also exhibits excellent antiviral activity against A/chicken/Hubei/327/2004 (H5N1-DW), which is superior to the reference drug OSC (EC[SUB]50[/SUB] = 5.97 μM). Molecular docking study shows that the thiophene moiety plays an essential role in compound 4b, which can bind well to the active site of NA. The good activity of 4b may be also ascribed to the extending of quinoline ring into the 150-cavity. The results of this study may provide an insightful help for the development of new NA inhibitors.
Keywords: 150-Cavity; Neuraminidase inhibitor; Thiophene; Virtual screening.