Produção Nacional
Revisado por pares
Aurones: A Promising Scaffold to Inhibit SARS-CoV-2 Replication
2023; American Chemical Society; Volume: 86; Issue: 6 Linguagem: Inglês
10.1021/acs.jnatprod.3c00249
ISSN1520-6025
AutoresGuilherme S. Caleffi, Alice dos Santos Rosa, Luana G. de Souza, João L. S. Avelar, Sarah Moreira Rodrigues do Nascimento, Vitor M. de Almeida, Amanda Resende Tucci, Vivian Neuza S. Ferreira, Alcides J. M. da Silva, Osvaldo A. Santos‐Filho, Milene Dias Miranda, Paulo R. R. Costa,
Tópico(s)Synthesis and biological activity
ResumoAurones are a small subgroup of flavonoids in which the basic C6–C3–C6 skeleton is arranged as (Z)-2-benzylidenebenzofuran-3(2H)-one. These compounds are structural isomers of flavones and flavonols, natural products reported as potent inhibitors of SARS-CoV-2 replication. Herein, we report the design, synthesis, and anti-SARS-CoV-2 activity of a series of 25 aurones bearing different oxygenated groups (OH, OCH3, OCH2OCH3, OCH2O, OCF2H, and OCH2C6H4R) at the A- and/or B-rings using cell-based screening assays. We observed that 12 of the 25 compounds exhibit EC50 < 3 μM (8e, 8h, 8j, 8k, 8l, 8m, 8p, 8q, 8r, 8w, 8x, and 8y), of which five presented EC50 < 1 μM (8h, 8m, 8p, 8q, and 8w) without evident cytotoxic effect in Calu-3 cells. The substitution of the A- and/or B-ring with OCH3, OCH2OCH3, and OCF2H groups seems beneficial for the antiviral activity, while the corresponding phenolic derivatives showed a significant decrease in the anti-SARS-CoV-2 activity. The most potent compound of the series, aurone 8q (EC50 = 0.4 μM, SI = 2441.3), is 2 to 3 times more effective than the polyphenolic flavonoids myricetin (2) and baicalein (1), respectively. Investigation of the five more active compounds as inhibitors of SARS-CoV-2 3CLpro based on molecular dynamic calculations suggested that these aurones should detach from the active site of 3CLpro, and, probably, they could bind to another SARS-CoV-2 protein target (either receptor or enzyme).
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