Synthesis, evaluation and structure-activity relationship studies of pterodontic acid acylated derivatives with anti-flu A virus (H1N1) activity in vitro.
Fitoterapia
; 177: 106133, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39067488
ABSTRACT
In order to develop antiviral drugs, we utilized pterodontic acid (Poa-1) as a lead compound and conducted various modifications, including oxidation, reduction, addition, esterification, and acylation, resulting in the synthesis of 29 derivatives, of which 25 were novel acylation derivatives. Cell-level validation demonstrated that 4 derivatives exhibited significant inhibitory effects on the influenza A virus (H1N1), with an IC50 = 4.04-36.13 µM. Notably, four acylation derivatives (compounds IIE5, IIE6, IIE9, and IIE17) exhibited specific antiviral activities against influenza A virus (H1N1) with low cytotoxicity, indicating favorable therapeutic indices (SI = 3.5-11.9). Structure-activity relationship studies indicated that C5-C6 olefins are essential groups for antiviral activity, C11-C12 conjugated olefins will not interfere with antiviral activity. Carboxylic acid is an essential group for activity. Moreoverï¼Carboxylic acid acylation can improve antiviral activity, and the inclusion of guanidine, cyclic amine, and phenyl groups with electron-donating substituents could enhance the antiviral activity of the lead compound. Natural products structural modifications are capable of improving the biological activity of lead compounds, offering a rapid pathway for the development of potent new structures.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Vírus da Influenza A Subtipo H1N1
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article