Synthesis and Biological Evaluation of 12N-substituted Tricyclic Matrinic Derivatives as a Novel Family of Anti-Influenza Agents.
Med Chem
; 14(8): 764-772, 2018.
Article
en En
| MEDLINE
| ID: mdl-29473520
ABSTRACT
BACKGROUND:
Influenza is still a serious threat to human health with significant morbidity and mortality, so it is desirable to develop novel anti-flu drug agents with novel structures.OBJECTIVE:
The main purpose of this research was to explore broad-spectrum anti-flu agents and provide antiviral stockpiles in response to potential future influenza pandemics.METHODS:
Fifteen novel 12N-substituted tricyclic matrinic derivatives were synthesized and evaluated for their anti-influenza activities against H1N1 subtype taking 12N-p-cyanobenzenesulfonyl matrinane (1) as the lead. All prepared compounds were characterized by 1H NMR, 13C NMR and ESI-HRMS. The pharmacokinetics (PK) profile of the key compound was also examined in this study.RESULT:
The structure-activity relationship study indicated that suitable benzyl groups on 12N atom might be beneficial for the activity. Among them, 12N-p-carboxybenzyl matrinic butane (17g) exhibited the most promising activity with an IC50 value of 16.2 µM and a selective index (SI) value of over 33.4. In addition, compound 17g displayed a good in vivo pharmacokinetic profile with an area under the curve (AUC0-∞) value of 9.89 µM·h.CONCLUSION:
We consider tricyclic matrinic butane derivatives to be a new class of anti-influenza agents and this study provided useful information on further optimization.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Quinolizinas
/
Alcaloides
/
Subtipo H1N1 del Virus de la Influenza A
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Med Chem
Asunto de la revista:
QUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China