Three bimetallic Cu–Ni nanoparticle-supported catalysts were synthesized by co-immobilization followed by H2 reduction. A chromium(III) terephthalate metal organic framework (MIL-101), titanium dioxide (TiO2), and carbon (C) with different properties (acidity and Brunauer–Emmett–Teller surface area) were selected as supports for studying the effect of the support nature on the catalytic activity and selectivity in the oxidation of benzyl alcohol. The physicochemical properties of the Cu–Ni-supported catalysts were characterized by XRD, NH3-TPD, nitrogen adsorption/desorption, TEM, EDS, XPS, and ICP-OES. Bimetallic Cu–Ni nanoparticles were highly dispersed on the support. The catalytic activities of CuNi/MIL-101, CuNi/TiO2, and CuNi/C were tested in the selective oxidation of benzyl alcohol to benzaldehyde in the presence of molecular oxygen under mild reaction conditions. The highest benzaldehyde yields were achieved with CuNi/TiO2, CuNi/MIL-101, and CuNi/C catalysts at 100 °C within 4 h under 5, 3, and 3 bar of O2, respectively. The bimetallic Cu–Ni-supported catalysts possessed two types of catalytic active sites: acid sites and bimetallic Cu–Ni nanoparticles. The CuNi/MIL-101 catalyst possessed a high number of acid sites and exhibited high yield during selective benzyl alcohol oxidation to benzaldehyde. Importantly, the catalysts exhibited a high functional group (electron-donating and electron-withdrawing groups) tolerance. Cu–Ni-supported catalysts with an Cu:Ni mole ratio of 1:1 exhibited the highest yield of 47% for the selective oxidation of benzyl alcohol to benzaldehyde. Reusability and leaching experiment results exhibited that CuNi/MIL-101 showed better stability than CuNi/TiO2 and CuNi/C catalysts due to the large porous cavities of MIL-101 support; these cavities can be used to trap bimetallic Cu–Ni nanoparticles and inhibit nanoparticle leaching.
A series of
N
-(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity against primary patient-derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds was evaluated against glioma cell lines, with compound
4j
exhibiting promising glioma growth inhibitory properties. Compound
4j
was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. AKT signalling is one of the main oncogenic pathways in glioma and is often targeted for novel therapeutics. Indeed, AKT2 levels correlated with glioma malignancy and poorer patient survival. Compound
4j
inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells and exhibited potent EC
50
against glioblastoma cell lines. Although exhibiting potency against glioma cells,
4j
exhibited significantly less cytotoxicity against non-cancerous cells even at fourfold–fivefold the concentration. Herein we establish a novel biochemical kinase inhibitory function for
N
-(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles and further report their anti-glioma activity
in vitro
for the first time.
KEY MESSAGE
Anti-glioma pyrano[2,3-c]pyrazole
4j
inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells.
4j
also displayed PKBβ/AKT2 inhibitory activity.
4j
is nontoxic towards non-cancerous cells.
A kalinite catalyzed direct synthesis of N-substituted 3-carbonylpyrroles from the Morita–Baylis–Hillman acetate of 2,2-dimethoxyacetaldehyde and a primary amine in ethanol was developed.
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