Synthesis and Biological Evaluation of Paclitaxel-aminoguanidine Conjugates for Suppressing Breast Cancer.

BACKGROUND: A combination of paclitaxel with antineoplastic agents or paclitaxel alone was used clinically for the treatment of metastatic breast cancer. However, paclitaxel has poor water solubility and limited effect on some metastatic breast cancers. Hence, novel paclitaxel derivatives are in demand. In addition, the inducible nitric oxide synthase inhibitor, and aminoguanidine has a synergistic antitumor effect with chemotherapeutics. OBJECTIVE: This study aims to design and synthesize the paclitaxel-aminoguanidine conjugates. Upon cellular internalization, the novel paclitaxel-aminoguanidine conjugates could release paclitaxel and aminoguanidine with the aid of esterase and weak acids in cancer cells. METHODS: Paclitaxel-aminoguanidine conjugates were synthesized using click chemistry. The biological activity of paclitaxel-aminoguanidine conjugates was evaluated by MTT assay, determination of nitric oxide, analysis of apoptosis and cell cycle, and wound healing assay. RESULTS: Here, a novel paclitaxel-aminoguanidine conjugate was synthesized using click chemistry. Compared with paclitaxel, the water solubility of paclitaxel-aminoguanidine conjugates increased obviously. Upon cellular internalization, the novel paclitaxel-aminoguanidine conjugates released paclitaxel and aminoguanidine to synergistically inhibit the proliferation and metastasis of breast cancer cells with the aid of esterase and weak acids in cancer cells. The results of the MTT assay showed that compared with paclitaxel or the mixture of paclitaxel and aminoguanidine, the cytotoxicity of compound 4 against 4T1 cells was enhanced. As for apoptosis induced by these compounds, the paclitaxel-aminoguanidine conjugates also had a stronger ability to induce apoptosis than paclitaxel or the mixture of paclitaxel and aminoguanidine. The results of the scratch test showed that the anti-metastatic effect of the conjugate was the strongest among these tested compounds. CONCLUSION: These findings indicate that paclitaxel-aminoguanidine conjugate is a promising anticancer agent worthy of further study.

Prediction of active marker of seabuckthorn polysaccharides for prevention and treatment of cervical cancer and mechanism study.

Objective: To predict the target of Seabuckthorn polysaccharides in the prevention and treatment of cervical cancer, and to explore its multi-target and multi-pathway mechanism. Methods: Using the Swisstarget database, a total of 61 potential targets of polysaccharide active components were obtained. Cervical cancer related targets were obtained from the GeneCards database. The correlation score was greater than 5 targets for 2727; 15 intersection targets of active ingredients and disease were obtained by Venn diagram. Cytoscape3.6.0 software was used to construct the Polysaccharide composition-Target-Disease Network and Protein-Protein Interaction Networks (PPI). Cytoscape3.6.0 software was used for visualization and network topology analysis to obtain core targets. Kyoto encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were analyzed using Metascape database. SailVina and PyMOL software were used for molecular docking to verify binding strength. Results: A total of 15 core targets were obtained for cervical cancer. These targets are significantly enriched in HIF-1 signaling pathway, Galactose metabolism, EGFR tyrosine kinase inhibitor resistance, growth factor receptor binding, carbohydrate binding, protein homodimerization activity and other GO and KEGG entries; Molecular docking showed that ADA and GLB1 were well bound to Glucose, D-Mannose, and Galactose. Conclusion: The effect of seabuckthorn polysaccharides on the prevention and treatment of cervical cancer is characterized by multi-component, multi-target and multi-pathway, which provides scientific basis for further research on the activity of seabuckthorn polysaccharides.

Optimization of the Artemisia Polysaccharide Fermentation Process by Aspergillus niger.

In order to investigate the fermentation process of Artemisia polysaccharides, this paper showcases an investigation into the effects of fermentation time, fermentation temperature, strain inoculum, Artemisia annua addition, and shaker speed on the polysaccharides production of Artemisia annua. The yield of Artemisia polysaccharides content was determined based on the optimization of single-factor test, and then a response surface test was conducted with temperature, inoculum, and time as response variables and the yield of Artemisia polysaccharides as response values. The fermentation process was then optimized and the antioxidant activity of Artemisia polysaccharides was monitored using DPPH, ABTS+, OH, and total reducing power. The optimum fermentation process was determined by the test to be 5% inoculum of Aspergillus niger, temperature 36°C, time 2 d, shaker speed 180 r/min, and 4% addition of Artemisia annua, and the extraction of Artemisia polysaccharides was up to 17.04% by this condition of fermentation. The polysaccharides from Artemisia annua fermented by Aspergillus Niger had scavenging effects on DPPH, ABTS, and OH free radicals.

Synthesis and Anti-cancer Activity of Paclitaxel-Coumarin Conjugate.

BACKGROUND: Paclitaxel, a natural diterpenoid compound, has anti-tumor effect by acting on tubulin, whereas coumarin, another kind of natural product, has anti-tumor effect, along with some other effects, such as anti-bacterial-., Moreover, it also possesses fluorescence. OBJECTIVE: Multi targeting is an effective strategy in drug design to combat tumor. Therefore, a combination of paclitaxel with other active molecular drugs for exploring the novel lead with multi-functions is in demand. MATERIALS AND METHODS: To synthsize paclitaxel-coumarin conjugate via click chemistry and to investigate anticancer activity by MTT assay and the scratch test. RESULTS AND DISCUSSION: The results of MTT assay showed that compared tothe paclitaxel, the anti-tumor activity of the conjugate was significantly improved. The results of flow cytometry showed that the conjugate had a stronger ability to induce apoptosis. The scratch test results showed that the conjugate had better anti- metastasis ability than paclitaxel. CONCLUSION: These findings indicated that paclitaxel and coumarin had a synergistic effect, which paved the way for the development of paclitaxel through fluorescence.

[Chemical constituents of Osmanthus fragrans].

By Silica gel, Sephadex LH-20 and other materials for isolation and purification and by physicochemical methods and spectral analysis for structural identification, 32 compounds were isolated and identified from ethyl acetate portion of alcohol extract of the Osmanthus fragrans. Their structures were identified as boschniakinic acid (1), ursolaldehyde (2), augustic acid (3), arjunolic acid (4), 5-hydroxymethyl-2-furancarboxaldehyde (5), isoscutellarein (6), 6, 7-dihydroxycoumarin (7), 2α-hydroxy-oleanolic acid (8), quercetin-3-0-ß-D-glu-copyranoside (9), D-allito (10), 5, 4'-dihydroxy-7- methoxyflavone-3-0-ß-D-glucopyranoside (11), 5,7-dihydroxychromone (12), lupeol (13), naringenin (14), acetyloleanolic acid (15), chlorogenic acid (16), kaempferol-3-0-ß- D-glucopyranoside (17), oleanolic acid (18), kaempferol-3-0-ß-D-galactopyanoside (19), 3', 7-dihydroxy-4'-methoxyisoflavon (20), ergosta-4,6,8 (14), 22-tetraen-3-one (21), p-hydroxycinnamic acid (22), syringaresinol (23), 3,4-dihydroxyacetophenonel (24), ß-sitosterol (25), ethyl p-hydroxyphenylacetate (26), benzoic acid (27), caffeic acid (28), coelonin (29), p-hydorxy-phenylacetic acid (30), p-hydroxyacetophenone (31), and methyl-p-hydroxphenylacetate (32). Except for compounds 2, 4, 5, 8-11, 13, 15, 18, 20, 25, and 27, the rest were isolated from the Osmanthus fragrans for the first time.

[Chemical Constituents of Paris polyphylla var. chinensis Aerial Parts].

OBJECTIVE: To study the chemical constituents of aerial parts of Paris polyphylla var. chinensis . METHODS: Aerial parts of Paris polyphylla var. chinensis was extracted with 95% EtOH, and separated and purified by silica gel, RP 18 and Sephadex LH-20 col- umn chromatography. The structures were identified by spectroscopic analysis. RESULTS: A total of ten compounds were isolated and iden- tified as ß-sitosterol (1) ergosta-7, 22-dien-3-one (2), ß-ecdysone (3), kaempferol (4), daucosterol (5) luteolin (6) calonysterone (7), luteolin-7-O-glucoside (8), quercetin (9), and 3ß, 5α, 9α-trihydroxyergosta-7, 22-dien-6-one (10). CONCLUSION: Compounds 2,6 and 10 are isolated from Paris polyphylla var. chinensis for the first time.

[Chemical Constituents of Citrus medica Fruit].

OBJECTIVE: To study the chemical constituents of Citrus medica fruit. METHODS: The fruit of Citrus medica was extracted with 95% EtOH, and the compounds were separated and purified by silica gel, RP-18 and Sephadex LH-20 column chromatography. The structures were identified by spectroscopic analysis. RESULTS: A total of 16 compounds were isolated and identified, including methyl ferulic acid (1), dihydro-N-caffeoyltyramine (2) acacetin (3), ß-ecdysterone (4), (-)-balanophonin (5), p-methoxy cinnamic acid (6), umbelliferone (7), ferulic acid (8), pyrocatechualdehyde (9), diosmetin (10), 4-methoxy salicylic acid (1), ß-amyrin acetate (12), epigallocatechin (13), betulinic acid (14), lupeol (15) and nicotinamide (16). CONCLUSION: All the compounds are isolated from the fruit of Citrus medica for the first time.