Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis

Bioassay-guided fractionation of the EtOH extract from the flowers of Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae) led to the isolation of a new cucurbitane-type triterpenoid, aquilarolide A (1), along with five known compounds (2–6). The structure of 1 was elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR) experiments and mass spectrometry (MS) data and theoretical calculations of its electronic circular dichroism (ECD) spectra. Aquilarolide A, cucurbitacin E (3), cucurbitacin B (4), and 7-hydroxy-6-methoxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one (6) showed significant cytotoxicity against human lung adenocarcinoma SPC-A-1, human lung squamous cell carcinoma NCI-H520, human lung adenocarcinoma A549, and paclitaxel-resistant A549 (A549/Taxol) cell lines. All four active compounds, with IC(50) values ranging from 0.002 to 0.91 μM, had better inhibitory activities against A549/Taxol cells than paclitaxel (IC(50) = 1.80 μM). Among them, cucurbitacin E (IC(50) = 0.002 μM) is the most active. Further studies are needed to evaluate their in vivo antitumor activities and to clarify their mechanisms. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13659-022-00334-3.