protopanaxadiol--(3beta-12beta)-isomer and Neoplasms

Two new dammarane-type triterpenes, namely ginsenoslaloside-I [3β,12β,24S-trihydroxy-dammara-20(22)E,25-diene-3-O-β-D-glucopyranoside, 1] and 20(S)-ginsenoside-Rh1-6'-acetate (2), together with twelve known compounds (3-14) were isolated from the alkaline hydrolysate of total saponins of the stems-leaves of Panax ginseng C.A. Meyer. Their chemical structures were elucidated by extensive spectroscopic analyses and comparison with the reported data. All 14 compounds were evaluated for their anti-proliferative activities against two human cancer cell lines (HL-60 and Hep-G2) and promotion activities of SIRT1. Compound 6 exhibited significant inhibitory activity in a concentration-dependent manner against HL-60 and Hep-G2 with the IC50 values of 10.32 and 24.33μM, respectively, and had comparable IC50 values with those of vinorelbine, a positive control agent. Meanwhile, compounds 1 and 6 were found to be a potential activator of SIRT1. The preliminary structure-activity relationship was also discussed based on the experimental data obtained.

Topics: Antineoplastic Agents, Phytogenic; Cell Proliferation; Enzyme Activation; Ginsenosides; Hep G2 Cells; HL-60 Cells; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Molecular Structure; Neoplasms; Panax; Plant Leaves; Plant Stems; Protein Hydrolysates; Saponins; Sirtuin 1

Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Docetaxel; Dose-Response Relationship, Drug; Doxorubicin; Drug Design; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms; Sapogenins; Taxoids; Verapamil

Five novel triterpenes were isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum and identified as gypensapogenin A (1), gypensapogenin B (2), gypensapogenin C (3), 3-O-β-d-glucopyranosyl-gypensapogenin D (4) and gypensapogenin D (5), two of which (1 and 2) possess unprecedented ring A. The cyclization of the side chains-3 formed five-membered cyclic ketone rings similar to ring E in 1. The 21-oic acid-21, 23-lactone was present in the side chains of 4 and 5. We also proposed the possible formation mechanisms of compounds 1-3. Compounds 1-5 were evaluated for cytotoxic activities in three cell lines including A549, U87 and Hep3B and compound 3 showed significant activities toward A549 and U87 human cancer cells (with IC 50 values at 0.11 and 0.58 μm respectively).

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cells, Cultured; Gynostemma; Humans; Magnetic Resonance Spectroscopy; Models, Chemical; Molecular Structure; Neoplasms; Plant Extracts; Quantitative Structure-Activity Relationship; Saponins; Triterpenes