Isolation of phenanthrenes and identification of phorbol ester derivatives as potential anti-CHIKV agents using FBMN and NAP from Sagotia racemosa

Abstract

Se seleccionó el extracto obtenido de la corteza del tallo de Sagotia racemosa por su potente actividad antiviral en un esfuerzo por identificar inhibidores de la replicación del virus Chikungunya (CHIKV). Utilizando un procedimiento clásico guiado por bioensayo, tres diterpenoides degradados no descritos en la literatura científica (trigohowiloles C y D y trigoflavidol D), así como trigoxifina K, ácido stictic, ácido hiperhomosekikaico y cinco flavonoides conocidos fueron aislados. Las estructuras de estos compuestos se dilucidaron mediante un amplio análisis de datos espectroscópicos de RMN. Aunque trigohowiloles C y D se aislaron de la fracción más activa, no mostraron ninguna actividad antiviral. Al usar las técnicas Feature-Based Molecular Networking (FBMN) y Network Annotation Propagation (NAP), se ha podido demostrar que la fuerte actividad anti-CHIKV encontrada para esta fracción podría deberse a la presencia de análogos de 12-tetradecanoylphorbol-13-acetato (TPA), uno de los inhibidores más potentes de la replicación del CHIKV identificado hasta la fecha.

In an effort to identify inhibitors of Chikungunya virus (CHIKV) replication, a systematic study of 594 extracts of plant species originating from the French Guiana plateau region was performed in a virus-cell-based assay for CHIKV assay. The extract obtained from the stem bark of Sagotia racemosa was selected for its potent antiviral activity. Using a classical bioassay-guided procedure, three undescribed degraded diterpenoids, i.e. trigohowilols C and D and trigoflavidol D, as well as trigoxyphin K, stictic acid, hyperhomosekikaic acid and five known flavonoids were isolated. The structures of these compounds were elucidated by extensive NMR spectroscopic data analysis. Although trigohowilols C and D were isolated from the most active fraction they didn't show any antiviral activity. By using the Feature-Based Molecular Networking (FBMN) and Network Annotation Propagation (NAP) workflows, it has been shown that the strong anti-CHIKV activity found for this fraction might be due to the presence of analogues of 12-O-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication identified to date.