tetano
Editor, Senior Moderator
Eur J Med Chem. 2020 May 4;199:112334. doi: 10.1016/j.ejmech.2020.112334. [Epub ahead of print]
Discovery of dihydropyrrolidones as novel inhibitors against influenza A virus.
Liu T[SUP]1[/SUP], Dai C[SUP]1[/SUP], Sang H[SUP]1[/SUP], Chen F[SUP]1[/SUP], Huang Y[SUP]1[/SUP], Liao H[SUP]1[/SUP], Liu S[SUP]1[/SUP], Zhu Q[SUP]2[/SUP], Yang J[SUP]3[/SUP].
Author information
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.
Copyright ? 2020 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Design and synthesis; Dihydropyrrolidones; Immunity regulation; Influenza a virus; Structure-activity relationship
PMID:32408213DOI:10.1016/j.ejmech.2020.112334
Discovery of dihydropyrrolidones as novel inhibitors against influenza A virus.
Liu T[SUP]1[/SUP], Dai C[SUP]1[/SUP], Sang H[SUP]1[/SUP], Chen F[SUP]1[/SUP], Huang Y[SUP]1[/SUP], Liao H[SUP]1[/SUP], Liu S[SUP]1[/SUP], Zhu Q[SUP]2[/SUP], Yang J[SUP]3[/SUP].
Author information
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.
Copyright ? 2020 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Design and synthesis; Dihydropyrrolidones; Immunity regulation; Influenza a virus; Structure-activity relationship
PMID:32408213DOI:10.1016/j.ejmech.2020.112334