Discovery of 2-Phenylquinolines with Broad-Spectrum Anti-coronavirus Activity.
ACS Med Chem Lett
; 13(5): 855-864, 2022 May 12.
Article
in English
| MEDLINE | ID: covidwho-1947205
ABSTRACT
A selection of compounds from a proprietary library, based on chemical diversity and various biological activities, was evaluated as potential inhibitors of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a phenotypic-based screening assay. A compound based on a 2-phenylquinoline scaffold emerged as the most promising hit, with EC50 and CC50 values of 6 and 18 µM, respectively. The subsequent selection of additional analogues, along with the synthesis of ad hoc derivatives, led to compounds that maintained low µM activity as inhibitors of SARS-CoV-2 replication and lacked cytotoxicity at 100 µM. In addition, the most promising congeners also show pronounced antiviral activity against the human coronaviruses HCoV-229E and HCoV-OC43, with EC50 values ranging from 0.2 to 9.4 µM. The presence of a 6,7-dimethoxytetrahydroisoquinoline group at the C-4 position of the 2-phenylquinoline core gave compound 6g that showed potent activity against SARS-CoV-2 helicase (nsp13), a highly conserved enzyme, highlighting a potentiality against emerging HCoVs outbreaks.
Full text:
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Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
Language:
English
Journal:
ACS Med Chem Lett
Year:
2022
Document Type:
Article
Affiliation country:
Acsmedchemlett.2c00123
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