Friedelane Triterpenes with Cytotoxic Activity from the Leaves of Maytenus quadrangulata (Celastraceae)

Three new triterpenes, 3,4-seco-3,11β-epoxyfriedel-4(23)-en-3β-ol (1), friedelan-3α,11β diol (2), 7β,26-epoxyfriedelan-3a,7a-diol (3), a mixture of two new triterpenes 3α-hydroxyfriedelan-29-yl palmitate (4) and 3α-hydroxyfriedelan-29-yl stearate (5) and eleven known compounds were obtained from the hexane extract of Maytenus quadrangulata leaves. The structures and the relative stereochemistry of the new triterpenes were established through 1D/2D nuclear magnetic resonance (NMR), high resolution mass spectrometry (HRMS), and Fourier transform infrared (FTIR) spectral data. The hexane extract and isolated compounds were submitted to the cytotoxicity assays against leukemia (THP-1 and K562), ovarian (TOV-21G) and breast cancer (MDA-MB-231) cell lines. Compounds 1, 2 and 11β-hydroxyfriedelan-3-one (15) displayed high cytotoxicity and selectivity against leukemic cells when compared to positive control cytarabine (for THP-1) and imatinib (for K562). Furthermore, compound 2 showed similar cytotoxicity and an enhanced selectivity towards ovarian and breast cells in comparison to positive control etoposide.

从四角美登木（Maytenus quadrangulata）叶片的正己烷提取物中，分离得到3个新三萜类化合物：3,4-断-3,11β-环氧羽扇-4(23)-烯-3β-醇（1）、羽扇烷-3α,11β-二醇（2）、7β,26-环氧羽扇烷-3α,7α-二醇（3），以及一对新三萜混合物：3α-羟基羽扇烷-29-基棕榈酸酯（4）与3α-羟基羽扇烷-29-基硬脂酸酯（5），另获得11个已知化合物。通过一维/二维核磁共振波谱（1D/2D Nuclear Magnetic Resonance, NMR）、高分辨质谱（High Resolution Mass Spectrometry, HRMS）及傅里叶变换红外光谱（Fourier Transform Infrared, FTIR）数据，明确了上述新三萜的结构及相对立体构型。对该正己烷提取物及分离得到的所有化合物，开展了针对白血病（THP-1、K562）、卵巢癌（TOV-21G）及乳腺癌（MDA-MB-231）细胞株的细胞毒性实验。与阳性对照阿糖胞苷（针对THP-1细胞）、伊马替尼（针对K562细胞）相比，化合物1、2及11β-羟基羽扇烷-3-酮（15）对白血病细胞展现出显著的细胞毒性与选择性。此外，相较于阳性对照依托泊苷，化合物2对卵巢癌及乳腺癌细胞株表现出相当的细胞毒性与更优的选择性。