ABSTRACT
In the present study, a series of 13-β-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.
Subject(s)
Humans , Antioxidants , Metabolism , Pharmacology , Cells, Cultured , Curcuma , Chemistry , Drug Stability , Drugs, Chinese Herbal , Chemistry , Pharmacology , Endothelium, Vascular , Cell Biology , Metabolism , Human Umbilical Vein Endothelial Cells , Hydrogen Peroxide , Metabolism , Malondialdehyde , Metabolism , Nitric Oxide , Metabolism , Oxidation-Reduction , Oxidative Stress , Phthalic Acids , Pharmacology , Sesquiterpenes , Pharmacology , Succinates , Pharmacology , Superoxide Dismutase , MetabolismABSTRACT
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.
Subject(s)
Humans , Antihypertensive Agents , Pharmacology , Therapeutic Uses , Biological Products , Pharmacology , Therapeutic Uses , Hypertension , Drug Therapy , Magnoliopsida , Chemistry , Peptides , Pharmacology , Therapeutic Uses , Phytochemicals , Pharmacology , Therapeutic Uses , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic UsesABSTRACT
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, β1-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 β1-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.