Synthesis of Scutellarein Derivatives with a Long Aliphatic Chain and Their Biological Evaluation against Human Cancer Cells

Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine Erigeron breviscapus (Vant.) Hand-Mazz., which is widely used in China. Recently, accumulating evidence has highlighted the potential role of scutellarin and its main metabolite scutellarein in the treatment of cancer. To explore novel anticancer agents with high efficiency, a series of new scutellarein derivatives with a long aliphatic chain were synthesized, and the antiproliferative activities against Jurkat, HCT-116 and MDA-MB-231 cancer cell lines were assessed. Among them, compound 6a exhibited the strongest antiproliferative effects on Jurkat (IC50 = 1.80 μM), HCT-116 (IC50 = 11.50 μM) and MDA-MB-231 (IC50 = 53.91 μM). In particular, 6a even showed stronger antiproliferative effects than the positive control NaAsO2 on Jurkat and HCT-116 cell lines. The results showed that a proper long aliphatic chain enhanced the antiproliferative activity of scutellarein

Design, Synthesis, and Biological Evaluation of Novel Benzofuran Derivatives Bearing N-Aryl Piperazine Moiety

A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been synthesized and screened in vitro for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and for anticancer activity against three human tumor cell lines. The results demonstrated that derivative 16 not only had inhibitory effect on the generation of NO (IC50 = 5.28 μM), but also showed satisfactory and selective cytotoxic activity against human lung cancer line (A549) and gastric cancer cell (SGC7901) (IC50 = 0.12 μM and 2.75 μM, respectively), which was identified as the most potent anti-inflammatory and anti-tumor agent in this study

Simultaneous Qualitation and Quantitation of Chlorogenic Acids in Kuding Tea Using Ultra-High-Performance Liquid Chromatography–Diode Array Detection Coupled with Linear Ion Trap–Orbitrap Mass Spectrometer

Kuding tea, the leaves of Ilex Kudingcha C.J. Tseng, has been applied for treating obesity, hypertension, cardiovascular disease, hyperlipidemia, and so on. The chlorogenic acids (CGAs) in Kuding tea have shown excellent antioxidative, antiobesity, anti-atherosclerotic and anticancer activities. Nevertheless, the chemical profiles of CGAs in Kuding tea have not been comprehensively studied yet, which hinders further quality control. In the present study, a sensitive ultra-high-performance liquid chromatography-diode array detection coupled with a linear ion trap-Orbitrap (UHPLC-DAD-LTQ-Orbitrap) method was established to screen and identify CGAs in Kuding tea. Six CGA standards were first analyzed in negative ion mode with a CID-MS/MS experiment and then the diagnostic product ions (DPIs) were summarized. According to the retention behavior in the RP-ODS column, accurate mass measurement, DPIs and relevant bibliography data, a total of 68 CGA candidates attributed to 12 categories were unambiguously or preliminarily screened and characterized within 18 min of chromatographic time. This was the first systematic report on the distribution of CGAs in Kuding tea. Meanwhile, the contents of 6 major CGAs in Kuding tea were also determined by the UHPLC-DAD method. All the results indicated that the established analytical method could be employed as an effective technique for the comprehensive and systematic characterization of CGAs and quality control of the botanic extracts or Chinese medicinal formulas that contain various CGAs

Roemerine Improves the Survival Rate of Septicemic BALB/c Mice by Increasing the Cell Membrane Permeability of Staphylococcus aureus.

Staphylococcus aureus is one of the most frequently occurring hospital- and community-associated pathogenic bacteria featuring high morbidity and mortality. The occurrence of methicillin-resistant S. aureus (MRSA) has increased persistently over the years. Therefore, developing novel anti-MRSA drugs to circumvent drug resistance of S. aureus is highly important. Roemerine, an aporphine alkaloid, has previously been reported to exhibit antibacterial activity. The present study aimed to investigate whether roemerine can maintain these activities against S.aureus in vivo and further explore the underlying mechanism. We found that roemerine is effective in vitro against four S. aureus strains as well as in vivo against MRSA insepticemic BALB/c mice. Furthermore, roemerine was found to increase cell membrane permeability in a concentration-dependent manner. These findings suggest that roemerine may be developed as a promising compound for treating S. aureus, especially methicillin-resistant strains of these bacteria

Activity of roemerine against MRSA XJ75302 in a mouse sepsis model.

<p>Survival of BALB/c mice inoculated by i.p. injection with MRSA XJ75302 and treated with 20 mg/kg roemerine, oxacillin, vancomycin or sterile water by i.p. administration. Values with statistical significance by the log-rank test are indicated by an asterisks: *<i>P</i><0.05, ***<i>P</i><0.001 versus Model group.</p

Roemerine-mediated bacterial membrane permeabilization (original magnification, ×1000).

<p>(A) Cultured <i>S</i>. <i>aureus</i> ATCC29213 was treated with 0, 32, 64 or 128 μg/mL of roemerine for 6 h, then were stained with the dyes SYTO 9 (which stains live bacteria) and propidium iodide (which stains dead bacteria). The stained bacteria were analyzed by fluorescence microscopy to assess viability. (B) The numbers indicate the percentages of live bacteria within <i>S</i>. <i>aureus</i> ATCC29213 after treatment with different concentrations of Roemerine. (C) The numbers indicate the percentages of dead bacteria within <i>S</i>. <i>aureus</i> ATCC29213 after treatment with different concentrations of Roemerine.</p

Concentration-dependent inhibition of roemerine on the growth of four <i>S</i>. <i>aureus</i>.

<p>Roemerine was added to cell cultures containing different tested strains to a final concentration 8, 16, 32, or 64 μg/mL, with addition of an equal volume of sterile water as a control. The growth curves for four tested strains were measured using a BioscreenC™ instrument in the absence and presence of different concentrations of roemerine. The sample frequency was one hour and data at time points are the means for three replicates. ROE, roemerine. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 versus Control.</p

Effects of roemerine on the growth of bacteria colonies.

<p>Roemerine, vancomycin and oxacillin were added to cell cultures containing <i>S</i>. <i>aureus</i> ATCC29213, MRSA XJ75302, Mu50, or LAC, respectively, with addition of an equal volume of sterile water as a control. Aliquots of each culture were collected at 0, 3, 6, 12, and 24 h, and were then diluted and inoculated on solid agar. The number of colony-forming units (CFUs) was calculated from the number of colonies growing on plates, and the data are the means for three replicates. CON, control; ROE, roemerine; VAN, vancomycin; OXA, oxacillin. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 versus Control.</p