Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, México.
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, México.
Molecules. 2019 Jun 26;24(13):2366. doi: 10.3390/molecules24132366.
Three polyisoprenoid alcohols were isolated from the leaves of Tournefortia hirsutissima by a bioassay-guided phytochemical investigation. The compounds were identified as 16-hydroxy-lycopersene (Compound 1), (Z,E,ω)-dodecaprenol (Compound 2) and (Z,E,ω)-tridecaprenol (Compound 3). Compound 1, an unusual polyisoprenoid, was characterized by 1D and 2D NMR. We also determined the absolute configuration at C-16 by the modified Mosher's method. The in vitro antiproliferative and anti-inflammatory activities of the isolated compounds were evaluated. Among isolates, Compound 1 moderately inhibited the nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. On the other hand, Compound 1 displayed selective antiproliferative activity against HeLa, PC3, HepG2 and Hep3B cancer cells and was less potent against IHH non-cancerous cells. Compound 1 in Hep3B cells showed significant inhibition of cell cycle progression increasing the sub-G phase, suggesting cell death. Acridine orange/ethidium bromide staining and Annexin V-FITC/PI staining demonstrated that cell death induced by Compound 1 in cells Hep3B was by apoptosis. Further study showed that apoptosis induced by Compound 1 in Hep3b cells is associated with the increase of the ratio of Bax/Bcl-2, and caspase 3/7 activation. These results suggest that Compound 1 induce apoptotic cell death by the mitochondrial pathway. To our knowledge, this is the first report about the presence of polyprenol Compounds 1-3 in T. hirsutissima, and the apoptotic and anti-inflammatory action of Compound 1.
三种多异戊二烯醇类化合物通过生物测定指导的植物化学研究从毛叶桐的叶子中分离得到。这些化合物被鉴定为 16-羟基番茄红素（化合物 1）、（Z,E,ω）-十二碳烯醇（化合物 2）和（Z,E,ω）-十三碳烯醇（化合物 3）。化合物 1 是一种不寻常的多异戊二烯，通过 1D 和 2D NMR 进行了表征。我们还通过改进的莫舍尔法确定了 C-16 的绝对构型。分离得到的化合物的体外增殖抑制和抗炎活性进行了评价。在分离得到的化合物中，化合物 1 对脂多糖（LPS）刺激的 RAW 264.7 细胞中一氧化氮的产生有中度抑制作用。另一方面，化合物 1 对 HeLa、PC3、HepG2 和 Hep3B 癌细胞具有选择性的增殖抑制活性，对 IHH 非癌细胞的活性较弱。化合物 1 在 Hep3B 细胞中显示出显著的细胞周期进展抑制作用，增加了亚 G1 期，提示细胞死亡。吖啶橙/溴化乙锭染色和 Annexin V-FITC/PI 染色表明，化合物 1 在 Hep3B 细胞中诱导的细胞死亡是通过细胞凋亡。进一步的研究表明，化合物 1 在 Hep3b 细胞中诱导的细胞凋亡与 Bax/Bcl-2 比值的增加以及 caspase 3/7 的激活有关。这些结果表明，化合物 1 通过线粒体途径诱导细胞凋亡。据我们所知，这是首次报道毛叶桐中存在多萜醇化合物 1-3，以及化合物 1 的促凋亡和抗炎作用。
