Abstract
ABSTRACT
The α‐mangostin (
MGT
) is a natural xanthone obtained from the pericarp of mangosteen fruit (
Garcinia mangostana
Linn.), possessing a widely reported biological activity, including anticancer, anti‐inflammatory, antibacterial, and antiviral properties. However, the impact of its free phenolic hydroxyl groups on achieving biological activity has not yet been evaluated. In this context, the present work isolated and characterized
MGT
from mangosteen and obtained the semisynthetic acetylated mangostin (
AcMGT
) to evaluate its drug‐likeness, interaction profile with the serine/threonine‐protein kinase AKT (isoform AKT1), and anticancer profile using in silico and in vitro approaches. The semisynthetic compound
AcMGT
is stable for up to 48 h under mimetic biological conditions; however, the acetylation decreased the anticancer profile of
MGT
in murine colon cancer, murine triple negative breast cancer, and human osteosarcoma cancer (CT26, 4T1, and U2OS, respectively), for example, from 7.55 ± 0.10 to 29.90 ± 1.20 µM in 4T1, which might be expected due to the decrease in the interactive profile with AKT1. The fluorescence microscopy indicated that acetylation reduced
MGT
's capacity to induce vacuolization in 4T1 cells, and the drug‐likeness prediction for
AcMGT
decreased markedly compared with the natural product, highlighting the importance of free phenolic hydroxyl groups in
MGT
for achieving the expected anticancer profile.