tetano
Editor, Senior Moderator
Eur J Med Chem
. 2020 May 4;199:112334.
doi: 10.1016/j.ejmech.2020.112334. Online ahead of print.
Discovery of Dihydropyrrolidones as Novel Inhibitors Against Influenza A Virus
Teng Liu[SUP] 1 [/SUP], Chenshu Dai[SUP] 1 [/SUP], Huiting Sang[SUP] 1 [/SUP], Fangzhao Chen[SUP] 1 [/SUP], Yingna Huang[SUP] 1 [/SUP], Hui Liao[SUP] 1 [/SUP], Shuwen Liu[SUP] 1 [/SUP], Qiuhua Zhu[SUP] 2 [/SUP], Jie Yang[SUP] 3 [/SUP]
Affiliations
Abstract
More effective prophylactic and therapeutic strategies to combat influenza viruses are urgently required worldwide because the conventional anti-influenza drugs are facing drug resistance. Here, dihydropyrrolidones (DHPs), the products of an efficient multi-components reaction, were found to possess good activities against influenza A virus (IAV). Primary structure-activity relationship indicated that the activities of DHPs were greatly influenced by substituents and four of them had IC[SUB]50[/SUB] values lower than 10 μM (DHPs 5-2, 8, 14 and 19: IC[SUB]50[/SUB] = 3.11-9.23 μM). The activities against multiple IAV strains and mechanism of DHPs were further investigated by using 5-2 (IC[SUB]50[/SUB] = 3.11 μM). It was found that 5-2 possessed antiviral effects against all the investigated subtypes of IAVs with the IC[SUB]50[/SUB] values from 3.11 to 7.13 μM. Moreover, 5-2 showed very low cytotoxicity with CC[SUB]50[/SUB] > 400 μM. Results of mechanism study indicated that 5-2 could efficiently inhibit replication of IAV, up-regulate the expression of key antiviral cytokines IFN-β and antiviral protein MxA, and suppress the production of the NDAPH oxidase NOX1 in MDCK cells. These results indicated that 5-2 could be used as a potential inhibitor against wide subtypes of IAVs.
Keywords: Design and synthesis; Dihydropyrrolidones; Immunity regulation; Influenza a virus; Structure-activity relationship.
. 2020 May 4;199:112334.
doi: 10.1016/j.ejmech.2020.112334. Online ahead of print.
Discovery of Dihydropyrrolidones as Novel Inhibitors Against Influenza A Virus
Teng Liu[SUP] 1 [/SUP], Chenshu Dai[SUP] 1 [/SUP], Huiting Sang[SUP] 1 [/SUP], Fangzhao Chen[SUP] 1 [/SUP], Yingna Huang[SUP] 1 [/SUP], Hui Liao[SUP] 1 [/SUP], Shuwen Liu[SUP] 1 [/SUP], Qiuhua Zhu[SUP] 2 [/SUP], Jie Yang[SUP] 3 [/SUP]
Affiliations
- PMID: 32408213
- DOI: 10.1016/j.ejmech.2020.112334
Abstract
More effective prophylactic and therapeutic strategies to combat influenza viruses are urgently required worldwide because the conventional anti-influenza drugs are facing drug resistance. Here, dihydropyrrolidones (DHPs), the products of an efficient multi-components reaction, were found to possess good activities against influenza A virus (IAV). Primary structure-activity relationship indicated that the activities of DHPs were greatly influenced by substituents and four of them had IC[SUB]50[/SUB] values lower than 10 μM (DHPs 5-2, 8, 14 and 19: IC[SUB]50[/SUB] = 3.11-9.23 μM). The activities against multiple IAV strains and mechanism of DHPs were further investigated by using 5-2 (IC[SUB]50[/SUB] = 3.11 μM). It was found that 5-2 possessed antiviral effects against all the investigated subtypes of IAVs with the IC[SUB]50[/SUB] values from 3.11 to 7.13 μM. Moreover, 5-2 showed very low cytotoxicity with CC[SUB]50[/SUB] > 400 μM. Results of mechanism study indicated that 5-2 could efficiently inhibit replication of IAV, up-regulate the expression of key antiviral cytokines IFN-β and antiviral protein MxA, and suppress the production of the NDAPH oxidase NOX1 in MDCK cells. These results indicated that 5-2 could be used as a potential inhibitor against wide subtypes of IAVs.
Keywords: Design and synthesis; Dihydropyrrolidones; Immunity regulation; Influenza a virus; Structure-activity relationship.