| Autor: |
Ashraf-Uz-Zaman M, Li X, Yao Y, Mishra CB, Moku BK, Song Y |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2023 Aug 10; Vol. 66 (15), pp. 10746-10760. Date of Electronic Publication: 2023 Jul 28. |
| DOI: |
10.1021/acs.jmedchem.3c00924 |
| Abstrakt: |
Dengue (DENV) and Zika (ZIKV) viruses are important human pathogens, causing ∼100 million symptomatic infections each year. These infections carry a 20-fold increased incidence of serious neurological diseases, such as microcephaly in newborns (for ZIKV) and Guillain-Barré syndrome. Moreover, DENV can develop serious and possibly life-threatening dengue hemorrhagic fever in certain patients. Patients recovered from one of the four serotypes of DENV are still susceptible to other serotypes with a higher likelihood of serious disease because of antibody-dependent enhancement. Except for mosquito control, there have been no antiviral drugs to prevent and treat ZIKV/DENV infections. Phenotypic screening found that 2,3,6-trisubstituted quinazolinone compounds are novel inhibitors of ZIKV replication. Fifty-four analogues were synthesized, and their structure-activity relationships are discussed. Additional testing shows that compounds 22 , 27 , and 47 exhibited broad and potent activities against ZIKV and DENV with EC 50 values as low as 86 nM with no significant cytotoxicity to mammalian cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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