Speciation of nickel,copper, zinc,and manganese in different edible nuts: a comparative study of molecular size distribution by SEC–UV–ICP–MS

Molecular size distribution patterns of Cu, Mn, Ni, and Zn were determined in several nut species by size-exclusion liquid chromatography (SEC) coupled on-line to UV and inductively coupled plasma mass spectrometry (ICP–MS) for detection. The molecular weight (MW) fractionation of the different metals was performed with a Superdex Peptide column, injecting 100 L of the extracted solutions. The association of the elements with different MW fractions was observed with sequential detection by UV and ICP–MS. Various separation conditions were evaluated to obtain proper resolution and reproducible results with the size-exclusion column. Complete MW information of the elemental fractions in the nut samples was obtained within a retention time of 30 min. Fractionation of the above mentioned elements was done in nine different nut species commonly found in commercial markets. Variability of the fractionation patterns for two different extraction media, 0.05 mol L^–1 NaOH and 0.05 mol L^–1 HCl, was evaluated for every nut sample. Differences in the elemental fractionation patterns were found depending on the extraction procedure, nut species, and the type of element studied. It was also observed that the elements studied showed predominant association with high MW fractions when extracted with basic solution whereas with acidic extraction media only low MW fractions were obtained.     

The inhibition profiles of 4'-acylpyrrole–5-fluoroindolin-2-ones with a C-3' side chain for VEGFR2, PDGFR-β, and FGFR-1 protein kinases

In this study, we reported the inhibition profiles of 4′-acylpyrrole–5-fluoroindolin-2-one 3 with a C-3′ side chain for VEGFR2, PDGFR-β, and FGFR-1 protein kinases. The pyrrole-fused cyclohexanone moiety provided 3 with the best potency to inhibit the three kinases, and the C-3′ side chains contributed to the different inhibition profiles of 3 . Compound 3b with a C-3′ 2-carboxylethyl side chain showed good potency for the three kinase (IC₅₀: 25–260 nM), and compound 3g with a N,N-dialkyl-2-carbamoylethyl side chain was more active for VEGFR2 (IC₅₀: 59 nM) and PDGFR-β (IC₅₀: 16 nM) than FGFR-1 (IC₅₀: 1.7 μM). The C-3′ 3-(dialkylamino)propyl side chain accomplished 3h – j as selective PDGFR-β inhibitors (IC₅₀: 7.8–13 nM). Compound 3b was further investigated and found potent to inhibit VEGF- and FGF-dependent cell proliferation with moderate in vivo anticancer activity. Results from docking simulations revealed that the interactions of 3b with VEGFR2 and FGFR-1 which could account for the different inhibition profiles of 3 .