Styryllactones in the leaves of Goniothalamus lanceolatus Miq., molecular networking and their anti-dengue activity In vitro and In silico.

Due to dengue fever's swift global expansion and the lack of effective antiviral remedies, it is crucial to discover and develop new antiviral drugs. The study aimed to assess the antiviral potential of the extract and fractions from the leaves of Goniothalamus lanceolatus Miq. (Annonaceae). New Guinea C strain DENV-2, at a multiplicity of infection of 0.4, was used to infect Vero cells. The assessment of antiviral effectiveness was conducted through the plaque reduction assay. Deep metabolome analysis of the active fraction identified nine styryllactones based on reference standards and eighteen styryllactones were further annotated through a molecular database search. One new 2 H -tetrahydropyran derivative, 3- epi -goniothalesdiol A (19), together with seven known styryllactones (8 , 11 , 14 , 16 , 17 , 18 , and 22) were isolated from the leaves of G. lanceolatus. The active bis-styryllactone goniolanceolatin A (22) with the highest selectivity index (SI) underwent further evaluation using quantitative reverse transcription qRT-PCR to determine the viral RNA level. The qRT-PCR data showed that the IC 50 value for the active compound was 5.07 µg/mL, and its corresponding SI value was 5.30. Following comprehensive docking studies, the bis-styryllactone derivative 22 showed potential binding interactions with crucial amino acids of the Envelope (E) of DENV proteins comparable to those of ribavirin. [Display omitted] • In vitro evaluation of Goniothalamus lanceolatus leaf dichloromethane (GLLD) extract showed the strongest anti-dengue activity. • One new 2H-tetrahydropyran derivative was successfully isolated from the leaves of G. lanceolatus during a bioactivity-directed. • In vitro and in silico evaluation of bis-styryl lactone isolated from the most active fraction of leaves of G. lanceolatus showed the most potential anti-dengue activity. [ABSTRACT FROM AUTHOR]