Rational modifications on a benzylidene-acrylohydrazide antiviral scaffold, synthesis and evaluation of bioactivity against Chikungunya virus
摘要:
Chikungunya virus is a re-emerging arbovirus transmitted to humans by Aedes mosquitoes, responsible for an acute febrile illness associated with painful and debilitating arthralgia, which can persist for several months or become chronic. Over the past few years, infection with this virus has spread worldwide with a previously unknown virulence. No specific antiviral treatments nor vaccines are currently available against this important pathogen. Starting from the structure of a class of selective anti-CHIKV agents previously identified in our research group, different modifications to this scaffold were rationally designed, and 69 novel small-molecule derivatives were synthesised and evaluated for their inhibition of Chikungunya virus replication in Vero cells. Further structure-activity relationships associated with this class of antiviral agents were elucidated for the original scaffolds, and novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these new structures as antivirals against Chikungunya virus. (C) 2018 Elsevier Masson SAS. All rights reserved.
Rational modifications on a benzylidene-acrylohydrazide antiviral scaffold, synthesis and evaluation of bioactivity against Chikungunya virus
摘要:
Chikungunya virus is a re-emerging arbovirus transmitted to humans by Aedes mosquitoes, responsible for an acute febrile illness associated with painful and debilitating arthralgia, which can persist for several months or become chronic. Over the past few years, infection with this virus has spread worldwide with a previously unknown virulence. No specific antiviral treatments nor vaccines are currently available against this important pathogen. Starting from the structure of a class of selective anti-CHIKV agents previously identified in our research group, different modifications to this scaffold were rationally designed, and 69 novel small-molecule derivatives were synthesised and evaluated for their inhibition of Chikungunya virus replication in Vero cells. Further structure-activity relationships associated with this class of antiviral agents were elucidated for the original scaffolds, and novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these new structures as antivirals against Chikungunya virus. (C) 2018 Elsevier Masson SAS. All rights reserved.
[EN] HDAC INHIBITOR COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] COMPOSÉS INHIBITEURS DE HDAC ET MÉTHODES DE TRAITEMENT
申请人:UNIV FLORIDA
公开号:WO2015153516A1
公开(公告)日:2015-10-08
The instant invention describes hydrazide-containing compounds having therapeutic activity, and methods of treating disorders such as cancer, tumors and cell proliferation related disorders, or affect cell differentiation, dedifferentiation or transdifferentiation.
申请人:University of Florida Research Foundation, Inc.
公开号:US20170174619A1
公开(公告)日:2017-06-22
The instant invention describes hydrazide-containing compounds having therapeutic activity, and methods of treating disorders such as cancer, tumors and cell proliferation related disorders, or affect cell differentiation, dedifferentiation or transdifferentiation.
Rational modifications on a benzylidene-acrylohydrazide antiviral scaffold, synthesis and evaluation of bioactivity against Chikungunya virus
Chikungunya virus is a re-emerging arbovirus transmitted to humans by Aedes mosquitoes, responsible for an acute febrile illness associated with painful and debilitating arthralgia, which can persist for several months or become chronic. Over the past few years, infection with this virus has spread worldwide with a previously unknown virulence. No specific antiviral treatments nor vaccines are currently available against this important pathogen. Starting from the structure of a class of selective anti-CHIKV agents previously identified in our research group, different modifications to this scaffold were rationally designed, and 69 novel small-molecule derivatives were synthesised and evaluated for their inhibition of Chikungunya virus replication in Vero cells. Further structure-activity relationships associated with this class of antiviral agents were elucidated for the original scaffolds, and novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these new structures as antivirals against Chikungunya virus. (C) 2018 Elsevier Masson SAS. All rights reserved.