Find in Library

Three polyisoprenoid alcohols were isolated from the leaves of <i>Tournefortia hirsutissima</i> by a bioassay-guided phytochemical investigation. The compounds were identified as 16-hydroxy-lycopersene (Compound <b>1</b>), (<i>Z</i>₈,<i>E</i>₃,&#969;)-dodecaprenol (Compound <b>2</b>) and (<i>Z</i>₉,<i>E</i>₃,&#969;)-tridecaprenol (Compound <b>3</b>). Compound <b>1</b>, an unusual polyisoprenoid, was characterized by 1D and 2D NMR. We also determined the absolute configuration at C-16 by the modified Mosher&#8217;s method. The in vitro antiproliferative and anti-inflammatory activities of the isolated compounds were evaluated. Among isolates, Compound <b>1</b> moderately inhibited the nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. On the other hand, Compound <b>1</b> displayed selective antiproliferative activity against HeLa, PC3, HepG2 and Hep3B cancer cells and was less potent against IHH non-cancerous cells. Compound <b>1</b> in Hep3B cells showed significant inhibition of cell cycle progression increasing the sub-G₁ phase, suggesting cell death. Acridine orange/ethidium bromide staining and Annexin V-FITC/PI staining demonstrated that cell death induced by Compound <b>1</b> in cells Hep3B was by apoptosis. Further study showed that apoptosis induced by Compound <b>1</b> 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 <b>1</b> induce apoptotic cell death by the mitochondrial pathway. To our knowledge, this is the first report about the presence of polyprenol Compounds <b>1</b>&#8722;<b>3</b> in <i>T. hirsutissima</i>, and the apoptotic and anti-inflammatory action of Compound <b>1</b>.