Synthesis, SARS-CoV-2 main protease inhibition, molecular docking and in silico ADME studies of furanochromene-quinoline hydrazone derivatives.
Bioorg Med Chem Lett
; 102: 129679, 2024 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-38423371
ABSTRACT
Seven furanochromene-quinoline derivatives containing a hydrazone linker were synthesized by condensing a furanochromene hydrazide with quinoline 2-, 3-, 4-, 5-, 6-, and 8-carbaldehydes, including 8-hydroxyquinoline-2-carbaldehye. Structure-activity correlations were investigated to determine the influence of the location of the hydrazone linker on the quinoline unit on SARS-CoV-2 Mpro enzyme inhibition. The 3-, 5-, 6- and 8-substituted derivatives showed moderate inhibition of SARS-CoV-2 Mpro with IC50 values ranging from 16 to 44 µM. Additionally, all of the derivatives showed strong interaction with the SARS-CoV-2 Mpro substrate binding pocket, with docking energy scores ranging from -8.0 to -8.5 kcal/mol. These values are comparable to that of N3 peptide (-8.1 kcal/mol) and more favorable than GC-373 (-7.6 kcal/mol) and ML-188 (-7.5 kcal/mol), all of which are known SARS-CoV-2 Mpro inhibitors. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) profiles indicate that the derivatives have good drug-likeness properties. Overall, this study highlights the potential of the furanochromene-quinoline hydrazone scaffold as a SARS-CoV-2 Mpro inhibitor.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Proteases 3C de Coronavírus
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COVID-19
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article