Synthesis and anti-hepatocellular carcinoma activity of novel O2-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid.

Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.

The Dark-Purple Tea Cultivar 'Ziyan' Accumulates a Large Amount of Delphinidin-Related Anthocyanins.

Recently, we developed a novel tea cultivar 'Ziyan' with distinct purple leaves. There was a significant correlation between leaf color and anthocyanin pigment content in the leaves. A distinct allocation of metabolic flow for B-ring trihydroxylated anthocyanins and catechins in 'Ziyan' was observed. Delphinidin, cyanidin, and pelargonidin (88.15 mg/100 g FW in total) but no other anthocyanin pigments were detected in 'Ziyan', and delphinidin (70.76 mg/100 g FW) was particularly predominant. An analysis of the catechin content in 'Ziyan' and eight other cultivars indicated that 'Ziyan' exhibits a preference for synthesizing B-ring trihydroxylated catechins (with a proportion of 74%). The full-length cDNA sequences of flavonoid pathway genes were isolated by RNA-Seq coupled with conventional TA cloning, and their expression patterns were characterized. Purple-leaved cultivars had lower amounts of total catechins, polyphenols, and water extract than ordinary non-anthocyanin cultivars but similar levels of caffeine. Because dark-purple-leaved Camellia species are rare in nature, this study provides new insights into the interplay between the accumulations of anthocyanins and other bioactive components in tea leaves.

Current natural products with antihypertensive activity.

Natural products have been an important source of new drugs, which also played a dominant role in the discovery and research of new drugs for the treatment of hypertension. This review article reviews the recent progress in the research and development of natural lead compounds with antihypertensive activity, including alkaloids, diterpenes, coumarins, flavonoids, and peptides. We summarized their structures, sources, as well as the antihypertensive mechanisms. These information provides instructive reference for the following structural modifications and optimization.

Synthesis of 13-ß-elemene ester derivatives and evaluation of their antioxidant activity in human umbilical vein endothelial cells.

In the present study, a series of 13-ß-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.

Synthesis and ß-adrenergic blocking activity of oxime ether hybrids derived from a natural isochroman-4-one.

AIM: In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized. METHOD: Compounds 3 and 6, derived from the natural antihypertensive compound 7, 8-dihydroxy-3-methyl-isochroman-4-one (XJP), were designed and synthesized. Subsequently, a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime. Furthermore, ß1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria. RESULTS: Twenty target compounds were obtained, and the preliminary structure-activity relationships were deduced. The most promising compound Ic exhibited ß1-adrenoceptor blocking activity (inhibition: 52.2%) at 10(-7) mol·L(-1), which was superior to that of propranolol (inhibition: 49.7%). CONCLUSION: The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.

Transformation of strictosamide to vincoside lactam by acid catalysis.

AIM: To identify the structure of the acid-catalyzed product of strictosamide and explore the reaction mechanism. METHODS: The acid-catalyzed reaction process of strictosamide was monitored by HPLC, and a macroporous resin was used to purify the reaction solution. The structure of the product was confirmed by MS, NMR, and ROESY spectra. RESULTS: The acid-catalyzed transformation yield from strictosamide to vincoside lactam was 52%. CONCLUSION: The reaction mechanism of the transformation from strictosamide to vincoside lactam may be related to the stability of the three-dimensional configuration of the compound. These results offer a new way to obtain vincoside lactam from the widely distributed indole alkaloid strictosamide by acid-catalysis.