In quest of small-molecules as potent non-competitive inhibitors against influenza.
Bioorg Chem
; 114: 105139, 2021 09.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1292618
ABSTRACT
A series of scaffolds namely aurones, 3-indolinones, 4-quinolones and cinnamic acid-piperazine hybrids, was designed, synthesized and investigated in vitro against influenza A/H1N1pdm09 virus. Designed molecules adopted different binding mode i.e., in 430-cavity of neuraminidase, unlike sialic acid and oseltamivir in molecular docking studies. All molecules reduced the viral titer and exhibited non-cytotoxicity along with cryo-protective property towards MDCK cells. Molecules (Z)-2-(3'-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2f), (Z)-2-(4'-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2g) and 2-(2'-Methoxy-phenyl)-1H-quinolin-4-one (3a) were the most interesting molecules identified in this research, endowed with robust potencies showing low-nanomolar EC50 values of 4.0 nM, 6.7 nM and 4.9 nM, respectively, compared to reference competitive and non-competitive inhibitors oseltamivir (EC50 = 12.7 nM) and quercetin (EC50 = 0.56 µM), respectively. Besides, 2f, 2g and 3a exhibited good neuraminidase inhibitory activity in sub-micromolar range (IC50 = 0.52 µM, 3.5 µM, 1.3 µM respectively). Moreover, these molecules were determined as non-competitive inhibitors similar to reference non-competitive inhibitor quercetin unlike reference competitive inhibitor oseltamivir in kinetics studies.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Subtipo H1N1 del Virus de la Influenza A
/
Bibliotecas de Moléculas Pequeñas
Idioma:
Inglés
Revista:
Bioorg Chem
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
J.bioorg.2021.105139
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