Vascular endothelial growth factor receptor (VEGFR-2), a member of the super family of protein tyrosine kinase receptors, plays a vital role in the regulation of tumor metastasis and angiogenesis. Several VEGFR-2 inhibitors have been marketed as antitumor drugs and a range of inhibitors are undergoing clinical or preclinical studies. According to the principle of multi-targeted pharmacolgy, in the field of tumor treatment, nonselective drugs targeting on more than one kinase to inhibit different cell pathways can be more effective than drugs specific for one kinase. Multi-target treatment does not mean abandonment of selectivity, but a precise selectivity for several kinases related to tumor, which is also a big challenge in the development of small molecular antitumor drugs. This paper reviews briefly the advances in research of the VEGFR-2 inhibitors and selectivity strategy in recent years.

Plumbagin (Plumbago zeylanica L.) has a wide spectrum of anticancer activity with a relatively lower toxicity. The molecular mechanisms of proliferation inhibition and apoptosis induction by plumbagin on esophageal squamous carcinoma cell lines may be important for the structure modification and clinical application of plumbagin. After treatment of KYSE-30, KYSE-70 and KYSE-140 cells with 0-20 μmol·L^-1 of plumbagin for 24, 48, 72 h, CCK8 was used to examine the proliferation, Annexin V and PI immunofluorescence staining for apoptosis, real-time PCR and Western blot for FoxM1 mRNA and protein expression, dual-luciferase reporter gene assay for the transcriptional activity of FoxM1, respectively. In addition, the relationship between anti-tumor effect of plumbagin and FoxM1 was investigated in vivo. Plumbagin significantly inhibited proliferation and induced apoptosis of esophageal squamous carcinoma cell in vitro and in vivo. Moreover, plumbagin down-regulated the expression of FoxM1 through suppression of its gene transcription. Our findings suggest that plumbagin may inhibit the proliferation of esophageal squamous carcinoma cell in vivo and in vitro through down-regulating the expression of FoxM1.

This study was aimed to construct a "drug-target-pathway" network of Xuebijing injection for sepsis treatment in an effort to explore the "multi-components, multi-targets, multi-pathways" mechanism based on "system-system" research mode. Active ingredients of Xuebijing injection were used to predict the potential targets according to reversed pharmacophore matching method. The pathway information was acquired from DAVID and KEGG database. The Cytoscape software was used to construct the "ingredient-target-pathway" network of Xuebijing injection for sepsis treatment. The results showed that 21 major active ingredients of Xuebijing injection regulated 550 targets (HRAS, GSK3B, BTK, AK, et al) and affected 10 inflammation and immune-related pathways, such as B cell receptor signaling pathway, VEGF signaling pathway, natural killer cell mediated cytotoxicity, Toll-like receptor signaling pathway. The sepsis therapeutic effect of Xuebijing injection reflected the action features of traditional Chinese medicine as multi-ingredients, multi-targets, multi-pathways. This research clarifies the material basis of Xuebijing injection for anti-inflammation and immunoregulation, providing a scientific basis for elucidation the mechanism of Xuebijing injection in the treatment of sepsis.

In this study, we developed a qualitative analytical method based on liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) for identification of multi-constituents of raw Fructus Arctii (RFA) and processed Fructus Arctii (PFA). We established a UHPLC-UV analytical method for simultaneously determining 6 major compounds in Fructus Arctii. UHPLC-Q-TOF-MS/MS qualitative analysis was performed under negative and positive ion modes and a total of 23 chemical compounds were identified. The analysis data were subjected to a principle component analysis with a t-test. Ten peaks were found to be the main difference (P < 0.05) between RFA and PFA. HPLC-UV quantitative method result showed the contents of 6 constituents were different between RFA and PFA. The results indicated that there was less arctiin, chlorogenic acid, isochlorogenic acid A in PFA than in RFA. However, there were higher levels of arctigenin, isochlorogenic acid B, isochlorogenic acid C in the PFA than RFA, which may be the main reason for different clinical efficacy of RFA and PFA.

The purpose of this study was to investigate the thermodynamics of naringenin (NAR)-isonicotinamide (INT) cocrystal (stoichiometric ratio, 1:2) formed in different solvents. The dissolution behavior of cocrystal was explored in the water. Solubility of NAR-INT cocrystals under various temperatures were measured, followed by fitting the complexation model to calculate the thermodynamic parameters solubility products (K_sp), complexation constants (K₁₂) and Gibbs energy change (ΔG) of cocrystal during formation progress. Ternary phase diagrams (TPDs) of the NAR-INT-solvent systems under various temperatures were plotted. Based on the non-linear simulation, 1:2 complexation model was well fitted to the NAR-INT cocrystal formation in ethanol, isopropanol and ethyl acetate, while no complexation model was more suitable for that in methanol. The cocrystallization reaction was exothermic and spontaneous (ΔG < 0, ΔH < 0, ΔS < 0). K_sp increased while K₁₂ decreased when increasing temperature, suggesting that the two components could cocrystallize more easily at the lower temperature. In comparison to TPDs in other solvents, the area of homogeneous liquid phase in ethyl acetate was the smallest, indicating the easiest formation of NAR-INT cocrystal in ethyl acetate. The current study provides a theoretical foundation for preparation and optimization of scale-up NAR-INT cocrystals.

Eighteen novel levofloxacin-thiadiazole HDACi conjugates were designed and synthesized from levofloxacin. The chemical structures of all conjugates were confirmed by ¹H NMR, ¹³C NMR and HR-MS spectra. The inhibitory activities of new conjugates were evaluated in an assay with a HDACs reagent kit, and their anti-tumor activities were tested in CCK-8 assay. The results showed that these new conjugates displayed potent inhibitory activity against HDACs, and the hydroxamate conjugates exhibited more potent activity than carboxylic acid and benzamide derivatives. Specifically, conjugate 5d exhibited the most potent anti-HDAC1 (IC₅₀=0.031±0.011 μmol·L^-1) and HDAC6 (IC₅₀=0.019±0.006 μmol·L^-1) activities, which was more potent than SAHA. Molecular docking studies suggest that the hydroxamate group of conjugate 5d was deeply inserted into the active site to interact with the residues in coordination with the zinc ion. Additionally, the thiadiazole group of conjugate 5d also engaged in hydrogen bonding with F679 in HDAC6, which had been linked to the selectivity of the HDAC isoforms. Moreover, these conjugates displayed significant antiproliferative effects on SW620, MGC-803, PC-3, NCIH460, MCF-7 and HepG2 cells, in particular, conjugate 5d showed the greatest potency against MGC-803 (IC₅₀=0.7±0.05 μmol·L^-1), NCIH460 (IC₅₀=2.3±0.421 μmol·L^-1), MCF-7 (IC₅₀=1.6±0.56 μmol·L^-1) and HepG2 (IC₅₀=3.9±0.26 μmol·L^-1), which was >3-fold more potent than SAHA. Additionally, all conjugates were nontoxic to health GES-1 cells, while SAHA showed some toxicity.

Due to the difference in structure and chemical properties of amino acids, it is difficult to determine amino acids with different properties by GC-MS. A method was established for the simultaneous determination of 20 amino acids by using ethyl chloroformate (ECF) as the derivatization reagent and adjusting pH 9-10 in the second derivatization in this study. The results showed that 20 amino acids were well separated and the compounds in the 2-20 μg·mL^-1 concentrations were detected with a good linear response correlation coefficient r² greater than 0.99. The results of precision and system adaptability show that RSD < 10%, the average recovery of samples in the 78.3%-109.9%. The results showed that the method was simple and easy to use, and the derivatization method could be carried out in aqueous solution. The derivatization product was stable with wide linear range, thus this method could be used for the determination of a variety of biological samples such as Astragalus mongolicus, mouse urine sample and mouse serum sample.

Neural stem cells (NSCs) posse the specialty of tumor tropism and be able to migrate specifically to tumor cells. NSCs are also cross the blood brain barrier. NSCs keep in touch with tumor cells preferentially under the tumor microenvironment, and surround the target cells. Based on these characteristics, NSCs can be used as a carrier for therapeutic virus, enzymes/prodrugs, genes or suicide genes, etc. which are selectively delivered to the glioma cells. NSCs may be modified by a variety of different genes to establish a reliable, safe and effective therapy for glioma.

Tianlongtongxin (TLTX) formula is composed of six Chinese herbs including Rhodiola rosea L., Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma and so on. It has been mainly used in the treatment of chest-Bi syndrome in the clinics. To investigate the material foundation and provide reference for clinical dosage regimen, the pharmacokinetics of seven components in the rat plasma were studied after oral administration of TLTX. A high sensitive method was established to determine the seven active components from TLTX in rat plasma based on the LC-MS/MS technique. The method met the requirements of preclinical pharmacokinetic study, through the investigation of linearity, specificity, recovery, accuracy, precision and stability. After administration of TLTX at 4.5 g·kg^-1 dose, all of the components were detectable in the plasma after 5 min. The concentration peaks were observed at 0.11-4.67 h respectively after administration with great difference in levels. The AUC of salidroside was significantly higher than other components, suggesting it as a main active component in TLTX formula. The observations provide scientific evidence for the rationality of salidroside as monarch drug in the formula.

Persicae semen has been used for years as a traditional Chinese medicine to treat diseases. Because of their similar morphologies, Persicae semen was commonly inadvertently mixed with Armeniacae semen amarum (a toxic herbal seed). Development of a reliable method for discriminating Persicae semen from its adulterant is necessary to reduce confusion for the drug safety in clinical practices. This study evaluates the efficiency of high-resolution melting (HRM) combined with internal transcribed spacer 2 (ITS2) to analyze Persicae semen. Our findings show that HRM allows not only the identification of adulteration but also the quantification of the most common admixture. HRM sensitivity in adulterant detection was assessed through the analysis of mixing samples with different proportions of Prunus persica and Prunus armeniaca control. The results are presented as a linear regression with r of 0.96 and imply the capability of the method to detect adulteration. In particular, HRM detected seeds of Prunus persica in Prunus armeniaca at concentrations as low as 1%, and commercial products labeled as 'Persicae semen' were purchased from markets and could rapid authenticated by HRM analyses. This study is significant in the verification of the authenticity in the quality control of herbal medicine. In the near future, it is promising to be the main trend for identifying traditional Chinese medicinal materials.