(E)-3-(4-Chloro­phen­yl)-1-(2-fur­yl)prop-2-en-1-one

In the title mol­ecule, C13H9ClO2, the benzene and furyl rings are slightly twisted from each other with a dihedral angle of 5.1 (1)°. An intra­molecular C—H⋯O hydrogen-bond inter­action generates an S(5) ring motif. In the crystal structure, mol­ecules are stacked along the b axis and the crystal packing is stabilized by weak inter­molecular C—H⋯O hydrogen bonds

(E)-3-(2-Chloro­phen­yl)-1-(3-methoxy­phen­yl)prop-2-en-1-one

The title compound, C16H13ClO2, adopts an E configuration with respect to the double bond of the propenone unit. The two benzene rings are twisted slightly from each other, making a dihedral angle of 7.14 (5)°. The mol­ecules are arranged in stacks, in which adjacent mol­ecules are related by inversion symmetry and form π–π inter­actions with a centroid–centroid distance of 3.7098 (6) Å. C—H⋯O and C—H⋯π inter­actions are formed between neighbouring mol­ecules

A Multi-Parametric Imaging Investigation of the Response of C6 Glioma Xenografts to MLN0518 (Tandutinib) Treatment.

Angiogenesis, the development of new blood vessels, is essential for tumour growth; this process is stimulated by the secretion of numerous growth factors including platelet derived growth factor (PDGF). PDGF signalling, through its receptor platelet derived growth factor receptor (PDGFR), is involved in vessel maturation, stimulation of angiogenesis and upregulation of other angiogenic factors, including vascular endothelial growth factor (VEGF). PDGFR is a promising target for anti-cancer therapy because it is expressed on both tumour cells and stromal cells associated with the vasculature. MLN0518 (tandutinib) is a potent inhibitor of type III receptor tyrosine kinases that demonstrates activity against PDGFRα/β, FLT3 and c-KIT. In this study a multi-parametric MRI and histopathological approach was used to interrogate changes in vascular haemodynamics, structural response and hypoxia in C6 glioma xenografts in response to treatment with MLN0518. The doubling time of tumours in mice treated with MLN0518 was significantly longer than tumours in vehicle treated mice. The perfused vessel area, number of alpha smooth muscle actin positive vessels and hypoxic area in MLN0518 treated tumours were also significantly lower after 10 days treatment. These changes were not accompanied by alterations in vessel calibre or fractional blood volume as assessed using susceptibility contrast MRI. Histological assessment of vessel size and total perfused area did not demonstrate any change with treatment. Intrinsic susceptibility MRI did not reveal any difference in baseline R2* or carbogen-induced change in R2*. Dynamic contrast-enhanced MRI revealed anti-vascular effects of MLN0518 following 3 days treatment. Hypoxia confers chemo- and radio-resistance, and alongside PDGF, is implicated in evasive resistance to agents targeted against VEGF signalling. PDGFR antagonists may improve potency and efficacy of other therapeutics in combination. This study highlights the challenges of identifying appropriate quantitative imaging response biomarkers in heterogeneous models, particularly considering the multifaceted roles of angiogenic growth factors

Sedimentary Accumulation of Black Carbon on the East Coast of The United States

The occurrence, trends and sources of soot black carbon (BC) in coastal sediments are poorly understood, particularly during the Anthropocene. Two sediment cores, covering the last ∼100 years from the US East Coast, off North Carolina and in the Florida Straits, were analyzed for organic carbon (OC), BC fluxes and BC sources. BC fluxes were 0.1 g cm−2 year−1 at both sites and accounted for 8%–22% of total OC. Carbon stable isotope values indicated OC to be of marine origin, while the BC was mostly terrestrially derived, C3-plant material. Radiocarbon values revealed BC originating mostly from fossil fuels or pre-aged carbon (fraction modern of 14%–31%) at North Carolina, while in the Florida Strait the BC was mostly derived from biomass burning (fraction modern of 70%–74%), in-line with continental (NC) or marine (FS) air mass origins. Ratios of polycyclic aromatic hydrocarbons broadly supported different BC sources at the two sites

4-Chloro-N′-[(Z)-4-(dimethyl­amino)benzyl­idene]benzohydrazide mono­hydrate

In the title compound, C16H16ClN3O·H2O, the dihedral angle between the two aromatic rings is 44.58 (11)°. The N atom of the dimethyl­amino group adopts a pyramidal configuration. In the crystal structure, mol­ecules are linked into a two-dimensional network parallel to the (001) plane by inter­molecular N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds involving the water mol­ecule and C—H⋯Cl hydrogen bonds. In addition, C—H⋯π inter­actions are observed

The HIF-pathway inhibitor NSC-134754 induces metabolic changes and anti-tumour activity while maintaining vascular function.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) mediates the transcriptional response to hypoxic stress, promoting tumour progression and survival. This study investigated the acute effects of the small-molecule HIF-pathway inhibitor NSC-134754. METHODS: Human PC-3LN5 prostate cancer cells were treated with NSC-134754 for 24 h in hypoxia. Orthotopic prostate tumour-bearing mice were treated with a single dose of NSC-134754 for 6, 24 or 48 h. Treatment response was measured using magnetic resonance spectroscopy and imaging. Ex-vivo histological validation of imaging findings was also sought. RESULTS: In vitro, NSC-134754 significantly reduced lactate production and glucose uptake (P<0.05), while significantly increasing intracellular glucose (P<0.01) and glutamine uptake/metabolism (P<0.05). Increased glutamine metabolism was independent of c-Myc, a factor also downregulated by NSC-134754. In vivo, a significantly higher tumour apparent diffusion coefficient was determined 24 h post-treatment (P<0.05), with significantly higher tumour necrosis after 48 h (P<0.05). NSC-134754-treated tumours revealed lower expression of HIF-1α and glucose transporter-1, at 6 and 24 h respectively, while a transient increase in tumour hypoxia was observed after 24 h. Vessel perfusion/flow and vascular endothelial growth factor levels were unchanged with treatment. CONCLUSION: NSC-134754 induces metabolic alterations in vitro and early anti-tumour activity in vivo, independent of changes in vascular function. Our data support the further evaluation of NSC-134754 as an anti-cancer agent

1-(2,4-Dichloro­phen­yl)-3-(4-methyl­phen­yl)prop-2-en-1-one

The mol­ecule of the title compound, C16H12Cl2O, adopts an E configuration. The dihedral angle between the two benzene rings is 42.09 (5)°. In the crystal structure, mol­ecules are linked into a three-dimensional framework by weak C—H⋯O inter­actions and by C—H⋯π inter­actions involving the methyl­phenyl ring

2,5-Dimethoxy­benzaldehyde thio­semicarbazone

In the title mol­ecule, C10H13N3O2S, the dihedral angle between benzene and –N—C(=S)—N—N=C– planes is 9.20 (6)°. The two meth­oxy groups are coplanar with the benzene ring [C—O—C—C torsion angles of −2.31 (18) and −6.45 (17)°]. In the crystal structure, mol­ecules are linked by inter­molecular N—H⋯S, N—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional network

4-[(4-Chloro­phen­yl)(5-hydr­oxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)meth­yl]-5-methyl-2-phenyl-1H-pyrazol-3(2H)-one

In the the title compound, C27H23ClN4O2, the chloro­phenyl ring forms dihedral angles of 77.70 (9) and 86.65 (9)°, respectively, with the pyrazol-3-one and pyrazole rings. The phenyl rings attached to the pyrazole rings are twisted away from them [dihedral angles 33.80 (9) and 40.34 (10)°]. An intramolecular O—H⋯O hydrogen bond generates an S(8) ring motif. The mol­ecules are linked into chains running along the c axis by N—H⋯N hydrogen bonds, and the chains are cross-linked via C—H⋯O hydrogen bonds and C—H⋯π inter­actions involving the chloro­phenyl ring