SB 218795

The effect of Sb-surfactant on GaInP CuPtB type ordering: assessment through dark field TEM and aberration corrected HAADF imaging.[Pubmed:28367549]

Phys Chem Chem Phys. 2017 Apr 12;19(15):9806-9810.

We report on the effect of Sb on the microstructure of GaInP layers grown by metal organic vapor phase epitaxy (MOVPE). These layers exhibit a CuPtB single variant ordering due to the intentional misorientation of the substrate (Ge(001) substrates with 6 degrees misorientation towards the nearest [111] axis). The use of Sb as a surfactant during the GaInP growth does not modify the type of ordering, but it is found that the order parameter (eta) decreases with increasing Sb flux. Dark field microscopy reveals a variation of the angle of the antiphase boundaries (APBs) with Sb amount. The microstructure is assessed through high angle annular dark field (HAADF) experiments and image simulation revealing Z-contrast loss in APBs due to the superposition of ordered domains.

Direct nucleation, morphology and compositional tuning of InAs1-x Sb x nanowires on InAs (111) B substrates.[Pubmed:28346221]

Nanotechnology. 2017 Apr 21;28(16):165601.

III-V ternary nanowires are interesting due to the possibility of modulating their physical and material properties by tuning their material composition. Amongst them InAs1-x Sb x nanowires are good candidates for applications such as Infrared detectors. However, this material has not been grown directly from substrates, in a large range of material compositions. Since the properties of ternaries are alterable by tuning their composition, it is beneficial to gain access to a wide range of composition tunability. Here we demonstrate direct nucleation and growth of InAs1-x Sb x nanowires from Au seed particles over a broad range of compositions (x = 0.08-0.75) for different diameters and surface densities by means of metalorganic vapor phase epitaxy. We investigate how the nucleation, morphology, solid phase Sb content, and growth rate of these nanowires depend on the particle dimensions, and on growth conditions such as the vapor phase composition, V/III ratio, and temperature. We show that the solid phase Sb content of the nanowires remains invariant towards changes of the In precursor flow. We also discuss that at relatively high In flows the growth mechanism alters from Au-seeded to what is referred to as semi In-seeded growth. This change enables growth of nanowires with a high solid phase Sb content of 0.75 that are not feasible via Au-seeded growth. Independent of the growth conditions and morphology, we report that the nanowire Sb content changes over their length, from lower Sb contents at the base, increasing to higher amounts towards the tip. We correlate the axial Sb content variations to the axial growth rate measured in situ. We also report spontaneous core-shell formation for Au-seeded nanowires, where the core is Sb-rich in comparison to the Sb-poor shell.

Differing Mechanisms of Death Induction by Fluorinated Taxane SB-T-12854 in Breast Cancer Cells.[Pubmed:28373418]

Anticancer Res. 2017 Apr;37(4):1581-1590.

BACKGROUND/AIM: Classical taxanes are routinely used in cancer therapy. In this study, mechanisms involved in death induction by the novel fluorine-containing taxane SB-T-12854 were investigated. MATERIALS AND METHODS: We employed breast cancer SK-BR-3, MCF-7 and T47D cell lines to assess activation of individual caspases, changes in the expression of proteins of the Bcl-2 family, and the release of pro-apoptotic factors from mitochondria into the cytosol after SB-T-12854 treatment. RESULTS: Caspase-2, -8, and -9 were activated in SK-BR-3 and MCF-7 cells. Only caspase-8 was activated in T47D cells. Caspase-7 and -6 were activated in all tested cells while caspase-3 was activated only in SK-BR-3 cells. Pro-apoptotic Bad protein seems to be important for cell death induction in all tested cells. Anti-apoptotic Bcl-2 and pro-apoptotic Bim, Bok, Bid and Bik seem to be also associated with cell death induction in some of the tested cells. The mitochondrial apoptotic pathway was significantly activated in association with the release of cytochrome c and Smac from mitochondria, but only in SK-BR-3 cells, not in MCF-7 and T47D cells. CONCLUSION: Cell death induced by SB-T-12854, in the tested breast cancer cells, differs regarding activation of caspases, changes in levels of pro-apoptotic and anti-apoptotic proteins of the Bcl-2 family and activation of the mitochondrial apoptotic pathway.

Critical evaluation of strategies for single and simultaneous determinations of As, Bi, Sb and Se by hydride generation inductively coupled plasma optical emission spectrometry.[Pubmed:28340714]

Talanta. 2017 May 15;167:217-226.

A systematic study of hydride generation (HG) of As, Bi, Sb and Se from solutions containing As(III), As(V), Bi(III), Sb(III), Sb(V), Se(IV) and Se(VI) was presented. Hydrides were generated in a gas-liquid phase separation system using a continuous flow vapor generation accessory (VGA) by mixing acidified aqueous sample, HCl and sodium borohydride reductant (NaBH4) solutions on-line. For detection, a simultaneous axially viewed inductively coupled plasma optical emission spectrometer (ICP-OES) was applied. Effects of the HCl concentration (related to sample and additional acid solutions) and type of the pre-reducing agents used for reduction of As(V), Sb(V) and Se(VI) into As(III), Sb(III) and Se(IV) on the analytical responses of As, Bi, Sb and Se were studied and discussed. Two compromised HG reaction conditions for simultaneous measurements of As+Bi+Sb (CC1) or As+Sb+Se (CC2) were established. It was found that choice of the pre-reductant prior to formation of the hydrides is critical in obtaining the dependable results of the analysis. Accordingly, for a As(III)+As(V)+Bi(III)+Sb(III)+Sb(V) mixture and using CC1, thiourea/thiourea-ascorbic acid interfered in Bi determination and hence, total As+Sb could be measured. If L-cysteine/L-cysteine-ascorbic acid were used, measurements of total Bi+Sb was possible in these HG reaction conditions. For a As(III)+As(V)+Sb(III)+Sb(V)+Se(IV)+Se(VI) mixture and using CC2, thiourea/thiourea-ascorbic acid and L-cysteine/L-cysteine-ascorbic acid influenced HG of Se but ensured total As+Sb determination. In contrast, heating a sample solution with HCl, although did not pre-reduce As(V) and Sb(V), assured quantitative reduction of Se(VI) to Se(IV). Finally, considering all favorable pre-reducing and HG conditions, methodologies for reliable determination of total As, Bi, Sb and Se by HG-ICP-OES were proposed. Strategies for single-, two- and three-element measurements were evaluated and validated, obtaining the detection limits (DLs) below 0.1ngg(-1) and precision typically in the range of 1.4-3.9% RSD.

Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 1. Identification of the 4-quinolinecarboxamide framework.[Pubmed:9191956]

J Med Chem. 1997 Jun 6;40(12):1794-807.

A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and clear structure-activity relationships (SARs) have been established. From SARs, (R)-N-[alpha-(methoxycarbonyl)benzyl]-2-phenylquinoline-4-carboxamide (65, SB 218795, hNK-3-CHO binding Ki = 13 nM) emerged as one of the most potent compounds of this novel class. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 65 is about 90-fold selective for hNK-3 versus hNK-2 receptors (hNK-2-CHO binding Ki = 1221 nM) and over 7000-fold selective versus hNK-1 receptors (hNK-1-CHO binding Ki = > 100 microM). In vitro functional studies in rabbit isolated iris sphincter muscle preparation demonstrated that 65 is a competitive antagonist of the contractile response induced by the potent and selective NK-3 receptor agonist senktide with a Kb = 43 nM. Overall, the data indicate that 65 is a potent and selective hNK-3 receptor antagonist and a useful lead for further chemical optimization.

In vitro and in vivo characterization of NK3 receptors in the rabbit eye by use of selective non-peptide NK3 receptor antagonists.[Pubmed:9351503]

Br J Pharmacol. 1997 Oct;122(3):469-76.

1. Inhibition of NK3 receptor agonist-induced contraction in the rabbit isolated iris sphincter muscle was used to assess the in vitro functional activity of three 2-phenyl-4-quinolinecarboxamides, members of a novel class of potent and selective non-peptide NK3 receptor antagonists. In addition, an in vivo correlate of this in vitro response, namely NK3 receptor agonist-induced miosis in conscious rabbits, was characterized with some of these antagonists. 2. In vitro senktide (succinyl-[Asp9,MePhe8]-substance P (6-11) and [MePhe7]-neurokinin B ([MePhe7]-NKB) were potent contractile agents in the rabbit iris sphincter muscle but exhibited quite different profiles. Senktide produced monophasic log concentration-effect curves with a mean pD2=9.03+/-0.06 and mean nH=1.2+/-0.02 (n=14). In contrast, [MePhe7]-NKB produced shallow log concentration-effect curves which often appeared biphasic (nH=0.54+/-0.04, n=8), preventing the accurate determination of pD2 values. 3. The contractile responses to the NK3 receptor agonist senktide were antagonized in a surmountable and concentration-dependent manner by SB 223412 ((-)-(S)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-ca rboxamide; 3-30 nM, pA2=8.4, slope=1.8+/-0.3, n=4). SB 222200 ((-)-(S)-N-(alpha-ethylbenzyl)-3-methyl-2-phenylquinoline-4-car box amide; 30-300 nM, pA2=7.9, slope=1.4+/-0.06, n=4) and SB 218795 ((-)-(R)-N-(alpha-methoxycarbonylbenzyl)-2-phenylquinoline-4-carboxamide; 0.3 and 3 microM apparent pKB=7.4+/-0.06, n=6). 4. Contractile responses to the NK3 receptor agonist [MePhe7]-NKB in the rabbit iris sphincter muscle were unaffected by SB 218795 (0.3 and 3 microM, n=8). In contrast, SB 223412 (30 and 300 microM n=4) and SB 222200 (0.3 and 3 microM, n=4) inhibited responses to low concentrations (< or = 1 nM), to a greater extent than higher concentrations (> 1 nM) of [MePhe7]-NKB. Furthermore, log concentration-effect curves to [MePhe7]-NKB became steeper and monophasic in the presence of each antagonist. 5. SB 218795 (3 microM, n=4) had no effect on contractions induced by transmural nerve stimulation (2 Hz) or substance P, exemplifying the selectivity of this class of antagonist for functional NK3 receptors over NK1 receptors in the rabbit. 6. In vivo, senktide (1, 10 and 25 microg i.v., i.e. 1.2, 11.9 and 29.7 nmol, respectively) induced concentration-dependent bilateral miosis in conscious rabbits (maximum pupillary constriction=4.25+/-0.25 mm; basal pupillary diameter 7.75+/-0.48 mm; n=4). The onset of miosis was within 2-5 min of application of senktide and responses lasted up to 30 min. Responses to two i.v. administrations of 25 microg senktide given 30 min apart revealed no evidence of tachyphylaxis. Topical administration of atropine (1%) to the eye enhanced pupillary responses to 25 microg senktide. This was probably due to the mydriatic effect of atropine since it significantly increased baseline pupillary diameter from 7.0+/-0.4 mm to 9.0+/-0.7 mm (n=4), thereby increasing the maximum capacity for miosis. Senktide-induced miosis was inhibited by SB 222200 (1 and 2 mg kg[-1], i.v., i.e. 2.63 and 5.26 micromol kg[-1]; maximum inhibition 100%; n=3-4), SB 223412 (0.5 and 1 mg kg[-1], i.v., i.e. 1.31 and 2.61 micromol kg[-1]; maximum inhibition 100%; n=3), SB 218795 (0.5 and 1 mg kg[-1] i.v., i.e. 1.26 and 2.52 micromol kg-1; maximum inhibition 78%; n=3), and the structurally distinct NK3 receptor antagonist SR 142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylep ipiperidin-4-yl)-N-methylacetamide; 1.5mg kg-1, i.v., i.e. 2.47micromol kg-1, maximum inhibition 92%; n=3). 7. Topical administration of senktide (25microg; 29.7nmol) to the eye induced unilateral miosis in the treated eye only. At this dose there was no significant difference (P<0.05) between pupillary constriction obtained by topical or i.v. senktide, and topically administered atropine had no significant effect on responses to topical senktide (n=4). 8. [MePhe7]-NKB (125, 250 and 500microg, i.v., i.e. 98.31, 196.62 and 393.24nmol, respectively) also induced bilateral miosis in conscious rabbits (maximum pupillary constriction=4.13+/-0.30mm; n=4), but in contrast to in vitro studies this agonist was approximately 100 fold less potent than senktide. [MePhe7]-NKB-induced miosis was inhibited by SB 222200 (5mg kg-1, i.v., i.e. 13.14micromol kg-1; maximum inhibition 69%; n=3). 9. In summary, SB 223412, SB 222200 and SB 218795 are potent and selective antagonists of NK3 receptor-mediated contraction in the rabbit isolated iris sphincter muscle. In addition, NK3 receptor agonist-induced miosis in conscious rabbits is a good in vivo correlate of the in vitro rabbit iris sphincter muscle preparation and appears to be a useful model for characterizing the pharmacodynamic profile and efficacy of structurally distinct NK3 receptor antagonists, such as SB 222200, SB 223412, SB 218795 and SR 142801.