Ligustrazine Derivatives Research Articles

Ligustrazine Derivatives. Part 8: Design, Synthesis, and Preliminary Biological Evaluation of Novel Ligustrazinyl Amides as Cardiovascular Agents

A series of novel Ligustrazinyl amides was designed, synthesized and evaluated for their protective effect on the injured vascular endothelial cells. The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured human umbilical vascular endothelial cells (HUVECs) that is damaged by hydrogen peroxide. Among the active compounds, compounds 8i, 8t and 8u exhibited the highest potency with low EC₅₀ values of 0.037, 0.070 and 0.055 mM, respectively. Structure-activity relationships were briefly discussed.

An overview on structural modifications of ligustrazine and biological evaluation of its synthetic derivatives

Ligustrazine, a natural product from Rhizoma Chuanxiong containing a pyrazine ring, has been widely used in China for treatment of heart diseases. Because of its remarkable effects but rapid metabolism, studies on structural modification of ligustrazine have attracted much attention. Ligustrazine synthetic derivatives reported in recent decades can be divided into ethers, esters, amides and piperazines, olefins, and others. These derivatives are mainly derived from four primary intermediates. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This paper is a compilation of almost all of the 304 synthetic ligustrazine derivatives we encountered; the information included is expected to be of benefit to further studies of ligustrazine.

Ligustrazine Derivatives. Part 6: Design, Synthesis and Evaluation of Novel Ligustrazinyl Acylguanidine Derivatives as Potential Cardiovascular Agents

A series of novel Ligustrazinyl acylguanidines was designed, synthesized and evaluated for their protective effect on injured vascular endothelial cell (ECV-304). The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured endothelial cell. Among the active compounds, compounds 8b, 8f and 8l displayed remarkable antioxidative activity with low EC(50) values of 0.097, 0.059 and 0.094 mM, respectively. Structure-activity relationships were briefly discussed.

Synthesis and Biological Evaluation of New Ligustrazine Derivatives as Anti-Tumor Agents

To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the “combination principle” in drug discovery. The ligustrazine derivatives’ anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 α,12 α-dihydroxy-5β-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD50 value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.

ChemInform Abstract: Ligustrazine Derivatives. Part 5. Design, Synthesis and Biological Evaluation of Novel Ligustrazinyloxy‐Cinnamic Acid Derivatives as Potent Cardiovascular Agents.

AbstractCompound (VIIIa) is found to be the most active anti‐platelet agent.

Ligustrazine Derivatives. Part 4: Design, Synthesis, and Biological Evaluation of Novel Ligustrazine‐based Stilbene Derivatives as Potential Cardiovascular Agents

A series of novel stilbene derivatives containing ligustrazinyl moiety was designed, synthesized, and assayed for their protective effects on damaged endothelial cells. The results showed that most ligustrazinyl stilbene derivatives exhibited high protective effects on the human umbilical vascular endothelial cells (HUVECs) damaged by hydrogen peroxide in comparison with Ligustrazine. The stilbene derivatives A6, A9, A11, A21, A24, A25, and A27 exhibited high potency with low EC(50) values ranged from 0.0249 μm to 0.0898 mm. Compound A27 displayed EC(50) 0.0249 μm, which is 30,000 times higher than that of Ligustrazine, presenting a most promising lead for further investigation. Structure-activity relationships were briefly discussed.

Ligustrazine derivatives. Part 5: Design, synthesis and biological evaluation of novel ligustrazinyloxy-cinnamic acid derivatives as potent cardiovascular agents

A series of novel ligustrazinyloxy-cinnamic acid derivatives were designed, synthesized and evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro, and also assayed for their protective effect against hydrogen peroxide (H2O2)-induced oxidative damage on ECV-304 cells. Some compounds exhibited high activity in one or both of the assays, of which, compound 2e displayed the highest protective effect on the proliferation of the damaged ECV-304 cells (EC50=0.020mM), and compound 2f was the most active anti-platelet aggregation agent (EC50=0.054mM). Structure–activity relationships were briefly discussed.

Synthesis of Novel Ligustrazine Derivatives as Na+/H+ Exchange Inhibitors

A novel series of 3,5,6-trimethylpyrazine-2-methoxy (or methylamino) substituted benzoyl-guanidine derivatives were designed and synthesized as Na(+)/H(+) exchange (NHE) inhibitors. In this study, compounds with electron-withdrawing substituents on the benzene ring seemed to improve NHE-1 inhibitory activities. Compounds 6d, 6k, and 6l were found to be potent inhibitors of NHE-1 (IC(50)=3.0±1.6, 3.0±1.4, and 1.6±0.4 nmol/l, resp.). Furthermore, they showed a remarkable reduction of infarct size in the rat myocardial infarction model in vivo.

Ligustrazine derivatives. Part 3: Design, synthesis and evaluation of novel acylpiperazinyl derivatives as potential cerebrocardiac vascular agents

A series of novel acylpiperazinyl Ligustrazine derivatives was designed, synthesized, and their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities were evaluated. The results showed that compound E33 displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound E1 was found to be the most active antiplatelet aggregation agent. Structure–activity relationships were briefly discussed.

Synthesis and NHE1 inhibitory activity of ligustrazine derivatives

A series of novel derivatives of ligustrazine linked with substituted benzoyl guanidine were synthesized. These compounds have not been reported in literature, and their chemical structures were confirmed by IR, 1H NMR and MS. The results of NHE1 inhibitory activity test showed that compounds I 2, I 3, I 4, I 6, and I 7 possess more potent NHE1 inhibitory activity than cariporide.

Herbal Medicine in Stroke

See related article, pages 1973–1979. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines, for which extensive observational and anecdotal experience has accumulated over the past thousand years. The World Health Organization (WHO) defines traditional medicine as “health practices, approaches, knowledge and beliefs incorporating plant, animal and mineral based medicines, spiritual therapies, manual techniques and exercises, applied singularly or in combination to treat, diagnose and prevent illnesses or maintain well-being”.1 Unlike Western medicine, which focuses on disease, traditional medicine takes the approach that the body provides external clues to an internal imbalance that can be addressed by interventions such as herbs and acupuncture (holistic treatment approach).2 According to a 2003 WHO report,1 traditional medicine is very popular in all developing countries, and its use is rapidly increasing in industrialized countries. For example, traditional herbal preparations account for 30% to 50% of the total medicinal consumption in China. In Europe, North America and other industrialized regions, over 50% of the population have used traditional medicine at least once. The global market for herbal medicines currently stands at over US $60 billion annually and is growing steadily.1 In recent years, several reviews have been published on the effect and potential benefits of traditional Eastern medicine in stroke.3–7 It has been suggested that some herbal medicines, or their products, may improve microcirculation in the brain,4,8 protect against ischemic reperfusion injury,8,9 possess neuroprotective properties3,4 and inhibit apoptosis,10 thus justifying their use in ischemic stroke patients. However, unlike industrially manufactured pharmacological drugs used in Western medicine, the active (potent) components of herbal medicines often have not been specified and measured precisely, although there have been recent attempts to regulate dosages and use of …

Design, synthesis, and biological activities of novel Ligustrazine derivatives

A series of novel Ligustrazine derivatives was designed, synthesized, and assayed for their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities. The results showed that most Ligustrazine derivatives exhibited lower EC 50 values for protective effects on the ECV-304 cells damaged by hydrogen peroxide in comparison with Ligustrazine. And some Ligustrazine derivatives presented better antiplatelet aggregation activities than Ligustrazine. The derivatives containing the bisphenylmethyl pharmacophore ( 7a– c) exhibited highest potency. Compound 7a displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound 7c was found to be the most active antiplatelet aggregation agent. Structure–activity relationships were briefly discussed.

The Preparation of Novel Ligustrazine Derivatives as Potential Cerebrocardiac Vascular Agents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

The Preparation of Novel Ligustrazine Derivatives as Potential Cerebrocardiac Vascular Agents

A series of novel substituted cinnamoylpiperazinyl ligustrazine derivatives 7 has been prepared by alkylation of cinnamoylpiperazines by (chloromethyl)trimethylpyrazine (5) or by cinnamoylation of trimethyl(piperazinomethyl) pyrazine (6).

Recent advances in the structural modification of ligustrazine: Cerebro- and cardiovascular activity of ligustrazine derivatives

Recent advances in the structural modification of ligustrazine and studies on the bioactivities of ligustrazine derivatives are reviewed in this article. Due to its rapid metabolism and short half-life, ligustrazine is not suitable for application in clinical practice. Derivatives of ligustrazine were therefore designed and synthesized, including ether, amine, amide, hydrocarbon and deuterated derivatives of ligustrazine and ester and alcohol derivatives of 2-hydroxymethyl-3,5,6-trimethylpyrazine, an active metabolite of ligustrazine. Some of these compounds present better cerebro- arid cardiovascular activities and more favorable pharmacokinetic properties compared to the parent compound.