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

Wang, Penglong; She, Gaimei; Yang, Yanan; Li, Qiang; Zhang, Honggui; Liu, Jie; Cao, Yinqiu; Xu, Xin; Lei, Haimin

doi:10.3390/molecules17054972

Cited by 54 publications

(62 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…(2). Compound 2 was prepared according to the method described by Wang et al and Li et al, with minor modifications [22,25]. To a solution of trimethylpyrazine (5.0 g, 36.8 mmol) in water (200 mL), aqueous potassium permanganate (KMnO 4 ) solution (8.6 g KMnO 4 :150 mL water) was added dropwise at room temperature over about 60 min.…”

Section: Chemistrymentioning

confidence: 99%

“…(1). Compound 1 was prepared according to our previously reported method [21]. The crude product, with 70% purity, was not purified further as it caused a strong mucous membrane irritation.…”

Section: Chemistrymentioning

confidence: 99%

“…As the important intermediates, 2-(bromomethyl)-3,5,6-trimethylpyrazine (1) and 3,5,6-trimethylpyrazine-2-carboxylic acid (2) were prepared according to our previous study [21,22]. In Scheme 1, typical synthetic procedures for 1a-5a involved the combination of bromo TMP and other hydroxybenzoic acids through the formation of ester and ether bonds under alkaline conditions, followed by hydrolysis of the corresponding ligustrazinyloxybenzoic acid esters 1a-5a in 20% (w/v) KOH aqueous solution, to obtain compounds 1b-5b.…”

Section: Chemistrymentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and Protective Effect of New Ligustrazine-Benzoic Acid Derivatives against CoCl2-Induced Neurotoxicity in Differentiated PC12 Cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

A series of novel ligustrazine-benzoic acid derivatives were synthesized and evaluated for their protective effect against cobalt chloride-induced neurotoxicity in differentiated PC12 cells. Combining hematoxylin and eosin staining, we found compound that (3,5,6-trimethylpyrazin-2-yl)methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (4a) displayed promising protective effect on the proliferation of the injured PC12 cells (EC 50 = 4.249 µM). Structure-activity relationships are briefly discussed.

show abstract

Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Protective Effect of New Ligustrazine-Benzoic Acid Derivatives against CoCl2-Induced Neurotoxicity in Differentiated PC12 Cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rigorous and systematic evaluations are, however, necessary to establish the efficacy of herbal formulas and transform traditional herbal practices into sciencebased medicines. [13][14][15][16][17] In the present article, we evaluated the anticancer activity of Ke formula, which has been shown to be effective in the clinic. The crude formula used in this study followed TCM treatment principles based on syndrome differentiation.…”

Section: Discussionmentioning

confidence: 99%

A Novel Herbal Formula Induces Cell Cycle Arrest and Apoptosis in Association With Suppressing the PI3K/AKT Pathway in Human Lung Cancer A549 Cells

et al. 2013

View full text Add to dashboard Cite

Aim of the study. In recent years, the incidence of lung cancer, as well as the mortality rate from this disease, has increased. Moreover, because of acquired drug resistance and adverse side effects, the effectiveness of current therapeutics used for the treatment of lung cancer has decreased significantly. Chinese medicine has been shown to have significant antitumor effects and is increasingly being used for the treatment of cancer. However, as the mechanisms of action for many Chinese medicines are undefined, the application of Chinese medicine for the treatment of cancer is limited. The formula tested has been used clinically by the China National Traditional Chinese Medicine Master, Professor Zhonging Zhou for treatment of cancer. In this article, we examine the efficacy of Ke formula in the treatment of non-small cell lung cancer and elucidate its mechanism of action. Methods. A Balb/c nude mouse xenograft model using A549 cells was previously established. The mice were randomly divided into normal, mock, Ke, cisplatin (DDP), and co-formulated (Ke + DDP) groups. After 15 days of drug administration, the animals were sacrificed, body weight and tumor volume were recorded, and the tumor-inhibiting rate was calculated. A cancer pathway finder polymerase chain reaction array was used to monitor the expression of 88 genes in tumor tissue samples. The potential antiproliferation mechanism was also investigated by Western blot analysis. Results. Ke formula minimized chemotherapy-related weight loss in tumor-bearing mice without exhibiting distinct toxicity. Ke formula also inhibited tumor growth, which was associated with the downregulation of genes in the PI3K/AKT, MAPK, and WNT/β-catenin pathways. The results from Western blot analyses further indicated that Ke blocked the cell cycle progression at the G1/S phase and induced apoptosis mainly via the PI3K/AKT pathway. Conclusion. Ke formula inhibits tumor growth in an A549 xenograft mouse model with no obvious side effects. Moreover, Ke exhibits synergistic antitumor effects when combined with DDP. The mechanism of action of Ke is to induce cell cycle arrest and apoptosis by suppressing the PI3K/AKT pathway. Further research will be required to determine the mechanism of action behind the synergistic effect of Ke and DDP.

show abstract

“…Analogously, the angiogenesis activities of S-CA were evaluated by a CAM assay ( Figure 2 and Table 2). The model was established according to our previous work [18].…”

Section: Angiogenesis Activitymentioning

confidence: 99%

New Synthesis Method for Sultone Derivatives: Synthesis, Crystal Structure and Biological Evaluation of S-CA

Yan

Zhang

et al. 2015

Molecules

Self Cite

View full text Add to dashboard Cite

There has been no remarkable progress in the synthesis of sultones in recent years. To facilitate more detailed studies of this functional group, we found a new method to synthesize the sulfonic acid lactone derivatives and finish its ring-closing reaction. A new sultone derivative, (E)-ethyl 4-oxo-6-styryl-3,4-dihydro-1,2-oxathiine-5-carboxylate 2,2-dioxide (S-CA), was synthesized and structurally identified by 1 H-NMR, 13 C-NMR, HMQC and X-ray single crystal diffraction analysis. The new rapid synthesis extended the method of ring-closing reaction of sulfonic acid lactone derivatives. The angiogenesis activities of S-CA were evaluated by the chick chorioallantoic membrane (CAM) model. It could selectively suppress small angiogenesis in CAM, without influencing either middle and large angiogenesis. In addition, anticancer efficacy of S-CA was evaluated in vivo using a murine sarcoma S180 model. Reduction of the tumor weight and tumor HE staining regions demonstrated that S-CA (10 mg/kg, intraperitoneal injection) had potent inhibition effects and a 44.71% inhibitory rate in S180 mice. Moreover, an acute toxicity test showed that the LD50 value of S-CA via intraperitoneal injection was 25.624 mg/kg.

show abstract

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

Cited by 54 publications

References 30 publications

Synthesis and Protective Effect of New Ligustrazine-Benzoic Acid Derivatives against CoCl2-Induced Neurotoxicity in Differentiated PC12 Cells

Synthesis and Protective Effect of New Ligustrazine-Benzoic Acid Derivatives against CoCl2-Induced Neurotoxicity in Differentiated PC12 Cells

A Novel Herbal Formula Induces Cell Cycle Arrest and Apoptosis in Association With Suppressing the PI3K/AKT Pathway in Human Lung Cancer A549 Cells

New Synthesis Method for Sultone Derivatives: Synthesis, Crystal Structure and Biological Evaluation of S-CA

Contact Info

Product

Resources

About