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European Journal of Medicinal Chemistry Sep 2020Enterovirus A71 (EV-A71) is a human pathogen causing hand, foot and mouth disease (HFMD) which seriously threatened the safety and lives of infants and young children....
Enterovirus A71 (EV-A71) is a human pathogen causing hand, foot and mouth disease (HFMD) which seriously threatened the safety and lives of infants and young children. However, there are no licensed direct antiviral agents to cure the HFMD. In this study, a series of quinoline formamide analogues as effective enterovirus inhibitors were developed, subsequent systematic structure-activity relationship (SAR) studies demonstrated that these quinoline formamide analogues exhibited good potency to treat EV-A71 infection. As described, the most efficient EV-A71 inhibitor 6i showed good anti-EV-A71 activity (EC = 1.238 μM) in RD cells. Furthermore, compound 6i could effectively prevent death of virus infected mice at dose of 6 mg/kg. When combined with emetine (0.1 mg/kg), this treatment could completely prevent the clinical symptoms and death of virus infected mice. Mechanism study indicated that compound 6i inhibited EV-A71 via targeting 2C helicase, thus impeding RNA remodeling and metabolism. Taken together, these data indicated that 6i is a promising EV-A71 inhibitor and worth extensive preclinical investigation as a lead compound.
Topics: Animals; Antiviral Agents; Dibucaine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enterovirus A, Human; Enterovirus Infections; Enzyme Inhibitors; Humans; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; RNA Helicases; Structure-Activity Relationship; Viral Proteins
PubMed: 32619885
DOI: 10.1016/j.ejmech.2020.112310 -
Contact Dermatitis Oct 2019
Topics: Adrenal Cortex Hormones; Anesthetics, Local; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dibucaine; Female; Humans; Middle Aged; Patch Tests; Phenylephrine
PubMed: 30977131
DOI: 10.1111/cod.13290 -
Contact Dermatitis Jun 2021
Topics: Adult; Austria; Dermatitis, Allergic Contact; Drug Combinations; Female; Germany; Humans; Male; Middle Aged; Patch Tests; Switzerland; para-Aminobenzoates
PubMed: 33400817
DOI: 10.1111/cod.13778