Chemical Constituents, Cytotoxicity, and Molecular Docking Studies of Tetragonula iridipennis Propolis

Abstract

Objective: Propolis of Tetragonula iridipennis, which is one of the most popular stingless bees found in Vietnam, has been used to promote health and prevent disease. This study aims to identify the chemical constituents of T iridipennis propolis and their cytotoxic activity. Methods: The propolis sample was extracted with ethanol. The crude extract was isolated by combined chromatographic methods. The structures of isolated compounds were determined by electrospray ionization mass spectrometry and nuclear magnetic resonance spectra. The cytotoxicity was evaluated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide method. The protein interactions of active compounds were explored by molecular docking study. Results: Sixteen known compounds, including 11 triterpenes, 3 xanthones, a sterol, and a flavonoid were isolated and identified. The propolis ethanol extract displayed good cytotoxicity against A-549 and KB cancer cell lines. 24 S,25-Dihydroxytirucall-7-en-3-one was the most active compound with IC50 values ranging from 18.75  ±  0.21 to 19.62  ±  0.36 µg/mL. Conclusions: Sixteen known constituents were identified from T. iridipennis propolis, of which 8 compounds were discovered for the first time. The propolis of T iridipennis has multiple sources of plant resin, among that Ailanthus triphysa (Simaroubaceae) was identified as a new plant source. A molecular docking study revealed that cytotoxic effects of 24 S,25-dihydroxytirucall-7-en-3-one, α-mangostin, 6-methoxy–bispyrano xanthone, and 3-isomangostin related to the inhibition of all 3 targets epidermal growth factor receptor, human epidermal growth factor receptor 2, and mammalian target of rapamycin (mTOR), while other isolated triterpenes exert their cytotoxicity by the inhibition of mTOR protein activity.