Garcinuntones A‒C, three new polyprenylated xanthones with cytotoxic and anti-HIV-1 activities from Garcinia nuntasaenii

Abstract

Three previously undescribed polyprenylated xanthone derivatives named garcinuntones A‒C (1 − 3), together with fifteen known compounds (4 − 18) were isolated from the leaves and twigs of Garcinia nuntasaenii Ngerns. & Suddee (Clusiaceae). Their structures were determined by analysis of their physical and spectroscopic data and by comparison with those of related compounds reported in the literature. The absolute configuration of garcinuntone B (2) was established by single crystal X-ray crystallographic analysis using Cu Kα radiation data. Cytotoxic activity against several cancer cell lines (P-388, KB, HT-29, MCF-7, A549, and ASK) and anti-HIV-1 activity using syncytium inhibition and anti-HIV-1 reverse transcriptase assays of some isolated compounds were evaluated. Garcinuntone B exhibited cytotoxicity against some tested cell lines with IC₅₀ values in the range of 4.82 to 6.92 μM. In anti-HIV-1 assays, garcinuntone B demonstrated selective activity against the reverse transcriptase (RT) enzyme, showing an IC₅₀ of 23.61 µM, while it proved to be toxic to the host cell line in the syncytium inhibition assay. In addition, the binding affinity of garcinuntone B to HIV-1 RT was assessed through molecular docking study. Like other non-nucleoside RT inhibitors, garcinuntone B showed stable number of contacts with the binding residues in the binding pocket of HIV-1 RT enzyme.

Graphical abstract