Synthesis and evaluation of enantiomers of hydroxychloroquine against SARS-CoV-2 in vitro

Autor: Xiangyu Zhang, Chunxiu Wu, Sheng Jiang, Youhua Xie, Ji Zhang, Jinbiao Liao, Yong Ni, Zhenlong Qian
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Drug
Male
remdesivir-TP
remdesivir triphosphate complex
viruses
media_common.quotation_subject
Clinical Biochemistry
MERS
Middle East Respiratory Syndrome
Pharmaceutical Science
Microbial Sensitivity Tests
Pharmacology
Biochemistry
Chemical synthesis
Antiviral Agents
Article
chemistry.chemical_compound
Mice
In vivo
Drug Discovery
Chlorocebus aethiops
medicine
Animals
Antiviral
Molecular Biology
Vero Cells
media_common
ComputingMethodologies_COMPUTERGRAPHICS
COVID-19
coronavirus disease 2019
Chemistry
SARS-CoV-2
Organic Chemistry
Drug Repositioning
COVID-19
Hydroxychloroquine
Stereoisomerism
Small molecule
Chiral resolution
r.t.
room temperature
Drug repositioning
FDA
U.S. Food and Drug Administration
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
Enantiomers
CPE
cytopathic effect
dpd
day post drug administration
Molecular Medicine
Female
Lead compound
medicine.drug
Zdroj: Bioorganic & Medicinal Chemistry
ISSN: 1464-3391
0968-0896
Popis: Graphical abstract
Since the end of 2019, the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic. There is an urgent need for effective and low-toxic antiviral drugs to remedy Remdesivir’s limitation. Hydroxychloroquine, a broad spectrum anti-viral drug, showed inhibitory activity against SARS-CoV-2 in some studies. Thus, we adopted a drug repurposing strategy, and further investigated hydroxychloroquine. We obtained different configurations of hydroxychloroquine side chains by using chiral resolution technique, and successfully furnished R-/S-hydroxychloroquine sulfate through chemical synthesis. The R configuration of hydroxychloroquine was found to exhibit higher antiviral activity (EC50 = 3.05 μM) and lower toxicity in vivo. Therefore, R-HCQ is a promising lead compound against SARS-CoV-2. Our research provides new strategy for the subsequent research on small molecule inhibitors against SARS-CoV-2.
Databáze: OpenAIRE
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