Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry* ; Sesquiterpenes/chemical synthesis* ; Molecular Structure ; Humans ; Liver Cirrhosis/genetics* ; Biomimetics ; Plant Extracts/pharmacology*

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.
Antioxidants ; chemical synthesis ; metabolism ; pharmacology ; Cells, Cultured ; Curcuma ; chemistry ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Endothelium, Vascular ; cytology ; drug effects ; metabolism ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Hydrogen Peroxide ; metabolism ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Phthalic Acids ; chemical synthesis ; pharmacology ; Sesquiterpenes ; chemical synthesis ; pharmacology ; Succinates ; chemical synthesis ; pharmacology ; Superoxide Dismutase ; metabolism

N-Acyl-4-phenylthiazole-2-amines were designed and synthesized, moreover their effects on acetylcholinesterase activities were tested. N-Acyl-4-phenylthiazole-2-amines were prepared from substituted 2-bromo-1-acetophenones by three steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The results showed that the target compounds had a certain inhibitory activity on AChE in vitro. Among them, 8c was the best, and IC50 of 8c was 0.51 micromol x L(-1), better than that of rivastigmine and Huperzine-A. The inhibitory activities of N-acyl-4-phenylthiazole-2-amines on acetylcholinesterase are worth while to be further studied.
Acetylcholinesterase ; metabolism ; Alkaloids ; pharmacology ; Amines ; chemical synthesis ; pharmacology ; Cholinesterase Inhibitors ; chemical synthesis ; pharmacology ; Drug Design ; Rivastigmine ; pharmacology ; Sesquiterpenes ; pharmacology ; Structure-Activity Relationship ; Thiazoles ; pharmacology

AIMTo search for new artemisinin derivatives with higher immunosuppressive activity.

METHODSTwo kinds of new artemisinin derivatives containing polyethylene glycol group were synthesized from dihydroartemisinin via condensation and esterification. These compounds were assayed for their inhibitory activity on ConA-induced T cell proliferation and LPS-induced B cell proliferation.

RESULTSTwenty three new compounds (2a - 2f, 3a - 3d, 4a - 4f, 6a, 6b and 7a - 7g) were synthesized and identified by 1H NMR and elemental analysis.

CONCLUSIONThese compounds had immunosuppressive activity in vitro. Among them, the symmetrical substituted compound 2 and 6 had higher activity than mono-substituted compound 3, 4 and 7. Especially, compounds 2a - 2f remarkably exhibited higher inhibition in comparison with artemisinin and artesunate.

Animals ; Artemisinins ; chemical synthesis ; pharmacology ; B-Lymphocytes ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Immunosuppressive Agents ; chemical synthesis ; pharmacology ; Molecular Structure ; Polyethylene Glycols ; Sesquiterpenes ; chemical synthesis ; pharmacology ; T-Lymphocytes ; drug effects

Animals ; Antimalarials ; chemical synthesis ; chemistry ; pharmacology ; Artemisinins ; chemical synthesis ; chemistry ; pharmacology ; Heterocyclic Compounds ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Plasmodium berghei ; drug effects ; Sesquiterpenes ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

AIMTo study asymmetric total synthesis of 14-nor-huperzine A 2 and its inhibitory activity on acetylcholinesterase.

METHODSHighly enantioselective synthesis of compound 5 from beta-keto-ester 3 and 2-methylene-1,3-propanediol diacetate 4 by palladium-catalyzed bicycloannulation was carried out using new chiral ferrocenylphosphine ligands, such as 10, 11, followed by regioselective double-bond migration to produce compound 6. Optically pure 6 was obtained after enantio-enrichment recrystallization. Then, according to similar procedures of huperzine A synthesis, the target compound 14-nor-huperzine A 2 was prepared. The inhibitory activity was tested with rat erythrocyte membrame acetylcholinesterase.

RESULTSThe inhibitory activity of synthetic (-)-14-nor-huperzine A was 8 fold less potent than that of (-)-huperzine A.

CONCLUSIONA hydrogen-bond between 14-methyl group of (-) huperzine A and the main-chain oxygen of His 440 is necessary for the highly acetylcholinesterase inhibitory activity of huperzine A.

Acetylcholinesterase ; metabolism ; Alkaloids ; Alzheimer Disease ; drug therapy ; Animals ; Cholinesterase Inhibitors ; chemical synthesis ; pharmacology ; therapeutic use ; Erythrocyte Membrane ; drug effects ; enzymology ; Molecular Conformation ; Molecular Structure ; Rats ; Sesquiterpenes ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use

Alkaloids ; Cholinesterase Inhibitors ; chemistry ; pharmacology ; Indans ; chemistry ; pharmacology ; Molecular Conformation ; Molecular Structure ; Piperidines ; chemistry ; pharmacology ; Sesquiterpenes ; chemical synthesis ; chemistry ; Tacrine ; chemistry