Organotin benzohydroxamate derivatives (OTBH) target colchicine-binding site exerting potent antitumor activity both in vitro and vivo revealed by quantitative proteomic analysis.

The activity of four typical organotin benzohydroxamate compounds (OTBH) with the different electronegativity of fluorine and chlorine atoms was assessed both in vitro and in vivo, revealing that they all exhibited notable antitumor effects. Furthermore, it was discovered that the biochemical capacity against cancer was influenced by their substituents' electronegativity and structural symmetry. For instance, benzohydroxamate derivatives with single chlorine at the fourth site on the benzene ring, two normal­butyl organic ligands, a symmetrical structure, and so on ([n-Bu2Sn[{4-ClC6H4C(O)NHO}2] (OTBH-1)) had stronger antitumor activity than others. Furthermore, the quantitative proteomic analysis discovered 203 proteins in HepG2 cells and 146 proteins in rat liver tissues that were differently identified before and after administration. Simultaneously, bioinformatics analysis of differentially expressed proteins demonstrated that the antiproliferative effects involved in the microtubule-based process, tight junction and its downstream apoptosis pathways. As predicted analytically, molecular docking indicated that ''-O-'' were the target docking atoms for the colchicine-binding site; meanwhile, this site was additionally verified by the EBI competition experiment and the microtubule assembly inhibition test. In conclusion, these derivatives promising for developing microtubule-targeting agents (MTAs) were shown to target the colchicine-binding site, impair cancer cell microtubule networks, and then halt mitosis and trigger apoptosis.

Isolation and Quantification of the Hepatoprotective Flavonoids From Scleromitron diffusum (Willd.) R. J. Wang With Bio-Enzymatic Method Against NAFLD by UPLC-MS/MS.

Flavonoids were the major phytochemicals against hepatic peroxidative injury in Scleromitron diffusum (Willd.) R. J. Wang with an inventive bio-enzymatic method by our group (LU500041). Firstly, the total flavonoids from Scleromitron diffusum (Willd.) R. J. Wang were extracted by reflux, ultrasonic, ultrasound-assisted enzymatic methods (TFH), and the bio-enzymatic method (Ey-TFH). Then 24 flavonoid compounds were isolated and quantified in the extracts by UPLC-MS/MS. Next, six representative differential compounds in Ey-TFH were further screened out by multivariate statistical analysis compared with those in TFH. In a further step, Ey-TFH presented a higher protective rate (59.30 ± 0.81%) against H2O2-damaged HL-02 hepatocytes than TFH. And six representative differential compounds at 8 and 16 µmol/L all exerted significant hepatoprotective effects (p < 0.05 or p < 0.01). Finally, the therapeutic action of Ey-TFH for nonalcoholic fatty liver disease (NAFLD) was processed by a rat's model induced with a high-fat diet. Ey-TFH (90, 120 mg/kg) significantly ameliorated the lipid accumulation in the rat model (p < 0.05). Meanwhile, Ey-TFH relieved liver damage. The levels of ALT, ALP, AST, LDH, and γ-GT in rats' serum were also significantly reduced (p < 0.05 or p < 0.01). In addition to this, the body's antioxidant capacity was improved with elevated SOD and GSH levels (p < 0.05) and down-regulated MDA content (p < 0.01) after Ey-TFH administration. Histopathological observations of staining confirmed the hepatic-protective effect of Ey-TFH.

Arsenic and nitrate remediation by isolated FeOB strains coupled with additional ferrous iron in the iron-deficient arid soils.

Remediation of As(III) by use of Fe(II) oxidation bacteria (FeOB) in iron-rich soils has been reported, but seldom used in the iron-deficient soil of arid areas. This study was aimed at selecting native bacterial strains to remediate As pollution in arid soils, coupled with the addition of Fe(II). The used methods included: The selection of two FeOB strains; XRD for solid phase identification based on peaks; SEM with EDS for morphology identification of newly formed minerals with chemical compositions; XPS for surface chemistry of the minerals; FTIR for functional groups of precipitates and 3DEEM for EPS determination, etc. The results were as follows: Sharp decrement curves of As(III) and NO3- with Fe(II) and total Fe contents and increment of NO2-; NH4+ fluctuating during the experimental period of 11 days; and precipitation of Fe(III) hydroxides together with As(III) with broken FeOBs due to encrustation in the SEM scan. It was concluded that two selected Pseudomonas strains have NAFO functionality by addition of iron as iron reduction-oxidation pair in the arid soil, further potentially fixing NH4+ while As(III) can be effectively remediated through the FeOB participation in forms of adsorption and co-precipitation of Fe(OH)3 through an oxidation of Fe(II) process.

Application of HPLC-Q/orbitrap MS in the detection and identification of anticancer constituents in ethyl acetate components from Hedyotis diffusa.

A feasible analytical method based on high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (HPLC-Q/orbitrap MS) has been established for the identification and characterization of anticancer constituents in ethyl acetate components from Hedyotis diffusa in our work. The mass spectrometer provided significant fragment information both in the full MS scan and data-dependent MS2 modes. Sixty-two possible compounds were analyzed and identified from the above results. Of the above 62 compounds, 12 have good separation in the positive ion mode, and 27 compounds have good separation in the anion mode. Currently, 39 have been reported in the literature related to the chemical composition of the plant, while the other 23 of the 62 compounds have not been reported. Fifteen tentatively identified compounds were given detailed descriptions. Four representative compounds from the ethyl acetate extract among the fifteen were actually isolated in good yield with silica gel column chromatography. Meanwhile, their structures were unambiguously identified as scopoletin, vanillic acid, p-coumaric acid and E-6-O-p-coumaroyl scandoside methyl ester using 1H NMR, 13C NMR, IR and UV spectroscopy. The purity of the ethyl acetate extracts, the total flavonoids, from Hedyotis diffusa could reach 65.6%. The inhibitory effect on HepG-2 cells of the total flavonoids was up to 66.2 ± 2.7%. Amentoflavone, quercetin, naringenin, and rutin were selected from the total flavonoids. The amentoflavone and quercetin had better hepatoprotective activity. The inhibition rates of 500 µmol L-1 amentoflavone and quercetin on HepG-2 cells could reach 56.2 ± 8.1% and 78.0 ± 9.3%, respectively. The EtOAc extracts could induce apoptosis in HepG2 cells by blocking the cell cycle in the G0/G1 phase. To the best of our knowledge, this is the first time that Q-orbitrap HRMS was applied to detect potential anticancer compounds in Hedyotis diffusa. This analytical method proved to be a feasible approach for the rapid detection of the potential anticancer compounds from Hedyotis diffusa.