Synthesis of 2-aryl substituted 2,3-dihydroquinazoline-4(1H)-ones under solvent free conditions using ionic liquid as a mild and efficient catalyst

A simple, green and environmentally benign procedure has been developed for the synthesis of 2,3-dihydroquinazoline-4(1H)-ones in basic ionic liquid via the cyclocondensation of 2-amino benzamide with an aldehyde. This offers several advantages such as high yields, simple procedure, low cost, short reaction times, mild and solvent free condition

N-[4-Cyano-3-(trifluoro­meth­yl)phen­yl]-2-eth­oxy­benzamide

In the title compound, C17H13F3N2O2, the two aromatic rings are essentially coplanar, forming a dihedral angle of 2.78 (12)°. The non-H atoms of the eth­oxy group are coplanar with the attached ring [maximum deviation = 0.271 (3) Å]. An intra­molecular N—H⋯O hydrogen bond occurs. In the crystal structure, mol­ecules are linked by inter­molecular C—H⋯N and C—H⋯F hydrogen bonds

Synthesis and biological evaluation of tetrahydropyridinepyrazoles ('PFPs') as inhibitors of STAT3 phosphorylation

The transcription factor STAT3 is constitutively overexpressed in many human tumors and hence represents a putative target for anticancer drug design. In this work, we describe the synthesis and biological evaluation of a novel chemotype, pyridine-fused pyrazoles ('PFPs') as inhibitors of STAT3 phosphorylation. The effect of the compounds synthesized was evaluated in cell proliferation assays of MCF-7 and HepG2 cancer cell lines and two of the compounds tested (12g and 12k) were found to show significant activity. Both compounds were also found to inhibit the proliferation of Hep3B, HUH-7 and PLC/PRF5 HCC cells in a dose-and time-dependent manner. Furthermore, we established in a DNA binding assay that one of the compounds (12g) was able to significantly inhibit the DNA binding ability of STAT3. Cytotoxicity of 12g against PC3 cells, which do not constitutively phosphorylate STAT3, was found to be minimal, hence lending further support for our mode-of-action hypothesis of this compound. We established for this structure a complete inhibition of CXCL12-induced cell invasion and associated wound healing in HCCLM3 cells, corroborating the proposed modulation of the STAT3 axis by 12g. Finally, molecular modeling was employed to evaluate the hypothesis of PFPs to bind to the SH2 domain of STAT3. Given the efficacy of PFPs in the biological systems studied here we propose their further evaluation in the context of STAT3-mediated cancer therapy

N-[4-Cyano-3-(trifluoro­meth­yl)phen­yl]-2-meth­oxy­benzamide

In the title compound, C16H11F3N2O2, the carboxamide group connecting the two aromatic rings is in a syn-periplanar configuration; the mol­ecule is non-planar; the dihedral angle between the two aromatic rings is 13.95 (18)°. Intra­molecular N—H⋯O and C—H⋯O hydrogen bonds occur. In the crystal, mol­ecules are linked by inter­molecular C—H⋯O hydrogen bonds

The past and future of enzyme measurements using surface enhanced Raman spectroscopy

The ability to accurately and sensitively measure the activity of specific enzymes is central to many aspects of modern chemistry and when combined with new nanoscience based approaches, offers significant opportunities for advancing other scientific disciplines. We review the development of surface enhanced resonance Raman scattering (SERRS) for the detection of enzymes, from the initial direct spectroscopy of enzymes, substrate/product and inhibitors adsorbed onto metallic colloids, to the current approach of measuring enzymatic activity by recording the SERRS spectra of a product which is only 'switched on' after enzyme activity. Developments focussed on improvements to modular masked SERRS substrates, which are unmasked by specific enzymes, are also reviewed. Finally, we set out the remaining grand challenges within the area of enzymatic analysis by SERRS which include single molecule detection, in vivo studies and increased multiplexing for screening of evolved enzyme libraries