Squeezing in Multivariate Spin Systems

In contrast to the canonically conjugate variates $q$,$p$ representing the position and momentum of a particle in the phase space distributions, the three Cartesian components, $J_{x}$,$J_{y}$, $J_{z}$ of a spin-$j$ system constitute the mutually non-commuting variates in the quasi-probabilistic spin distributions. It can be shown that a univariate spin distribution is never squeezed and one needs to look into either bivariate or trivariate distributions for signatures of squeezing. Several such distributions result if one considers different characteristic functions or moments based on various correspondence rules. As an example, discrete probability distribution for an arbitrary spin-1 assembly is constructed using Wigner-Weyl and Margenau-Hill correspondence rules. It is also shown that a trivariate spin-1 assembly resulting from the exposure of nucleus with non-zero quadrupole moment to combined electric quadrupole field and dipole magnetic field exhibits squeezing in cerain cases.Comment: 13 pages, 1 Table, Presented at ICSSUR-05, Franc

Synthesis and analysis of structural features of phenoxazine analogues needed to reverse vinblastine resistance in multidrug resistant ( MDR ) cancer cells

243-259In an attempt to find clinically useful modulators of multidrug resistance (MDR), a series of twentyone 2-chloro-N10-substituted phenoxazines has been synthesized. The novel 2-chlorophenoxazine is prepared by the pyrolytic condensation of 2-bromophenol and 2,5-dichloronitrobenzene. This compound undergoes N-alkylation in the presence of phase transfer catalyst (PTC). Stirring of 2-chlorophenoxazine with 1-bromo-3-chloropropane or l-bromo-4-chlorobutane in a two phase system consisting of an organic solvent (benzene) and 6N potassium hydroxide in the presence of tetrabutylammonium bromide leads to the formation of compounds 2 and 9 in good yield. N-(ω-chloroalkyl) and N-(chloroacetyl) analogues have been found to undergo iodide-catalyzed nucleophilic substitution on reaction with various secondary amines. Products have been characterized by UV, IR, 1H and 13C NMR, mass-spectral data and elemental analyses. The lipophilicity expressed in log10 P, and pKa of compounds have been determined. All the compounds have been examined for their ability to increase the uptake of vinblastine (VLB) in MDR KBChR-8-5 cells and the results show that compounds 3, 4, 7, 8 and 10-15 at 100 μM concentration exhibit enhanced accumulation of VLB by 2.0-5.8-fold greater than a similar concentration of verapamil. However, the effects on VLB uptake are specific because these derivatives have little activity in the parental drug-sensitive line KB 3-1. The effect of these compounds on the cellular accumulation of VLB in low P-glycoprotein containing MDR rhabdomyosarcoma cell line (Rh30) has also been examined. Most of the chlorophenoxazines at 100 μM concentration except 2, 9, 16 and 18 enhance significantly the accumulation of VLB in Rh30 cells by 10.9-53-fold with respect to control. Substitution of hydrogen by chlorine in position C-2 of the phenoxazine ring increases the ability to enhance the uptake of VLB in KBChR-8-5 cells by 1.15-19.7-fold. The effect of compounds 3, 5, 6, 12 and 17-21 on the efflux of VLB from KBChR-8-5 cells has been examined and the results show that these compounds except 21 significantly inhibit the efflux of VLB consistent with being competitors for P-glycoprotein. Efflux of VLB from Rh30 cells in the presence of 100 μM of 1, 5, 12, 17, 20 and 21 result in 43-65% of the accumulated VLB being retained at 2 hr, suggesting that the phenoxazines have relatively little effect on VLB efflux from Rh30 cells. The previous work using DiOC3 (3) has shown that the dye is a part of P-glycoprotein-mediated MDR phenotype. The KBChR-8-5 cells are loaded with 360 nM of DiOC3 (3) and efflux experiments are done in the absence or presence of 6, 12, or 21 by monitoring the fluorescence signal with time and the results in almost no efflux of the dye from the cells. These efflux data in KBChR-8-5 and Rh30 cells suggest that 2-chlorophenoxazines may act through both P-glycoprotein mediated and independent mechanisms. Cytotoxicity has been determined and the IC50 values lie in the range 3.2-42.1 μM for N10-chloropropyl, 2.7-16.7 μM for N10-chlorobutyl and 51.6-68.6 μM for N10-chloroacetyl derivatives against KBChR-8-5 cells suggesting that the antiproliferative activity decreases in the order: - butyl > - propyl > - acetyl analogues. Further, substitution of hydrogen by chlorine in C-2 of phenoxazine ring causes a greater enhancement in the antiproliferative potency by 1.1-2.6-fold for KBChR-8-5 cells than their respective counterparts, presumably due to increased hydrophobicity. Compounds at IC10 have been evaluated for their efficacy to modulate the cytotoxicity of VLB in KBChR-8-5 cells and compound 6 exhibits the greatest MDR reversal effect (136-fold) followed by compounds 12, 10, 13, 11 and so on. The structural features for reversal of MDR seem to include a hydrophobic phenoxazine ring with a -Cl group in the C-2 position and a tertiary amino group at a distance of three or four carbon chain from the tricyclic ring. Examination of the relationship between partition coefficient and cytotoxicity or antiMDR activity shows no correlation suggesting that lipophilicity is not the sole determinant of potency for biological activity

Synthesis and analysis of structural features of phenoxazine analogues needed to reverse vinblastine resistance in multidrug resistant (MDR) cancer cells

In an attempt to find clinically useful modulators of multidrug resistance (MDR), a series of twentyone 2-chloro-N-10-substituted phenoxazines has been synthesized. The novel 2-chlorophenoxazine is prepared by the pyrolytic condensation of 2-bromophenol and 2,5-dichloronitrobenzene. This compound undergoes N-alkylation in the presence of phase transfer catalyst (PTC). Stirring of 2-chlorophenoxazine with 1-bromo-3-chloropropane or 1-bromo-4-chlorobutane in a two phase system consisting of an organic solvent (benzene) and 6N potassium hydroxide in the presence of tetrabutylammonium bromide leads to the formation of compounds 2 and 9 in good yield. N-(omega -chloroalkyl) and N-(chloroacetyl) analogues have been found to undergo iodide-catalyzed nucleophilic substitution on reaction with various secondary amines. Products have been characterized by UV, IR, H-1 and C-13 NMR, mass-spectral data and elemental analyses. The lipophilicity expressed in log(10) P, and pK(a) of compounds have been determined. All the compounds have been examined for their ability to increase the uptake of vinblastine (VLB) in MDR KBCh(R)-8-5 cells and the results show that compounds 3, 4, 7, 8 and 10-15 at 100 muM concentration exhibit enhanced accumulation of VLB by 2.0-5.8-fold greater than a similar concentration of verapamil. However, the effects on VLB uptake are specific because these derivatives have little activity in the parental drug-sensitive line KB 3-1. The effect of these compounds on the cellular accumulation of VLB in low P-glycoprotein containing MDR rhabdomyosarcoma cell line (Rh30) has also been examined. Most of the chlorophenoxazines at 100 muM concentration except 2, 9, 16 and 18 enhance significantly the accumulation of VLB in Rh30 cells by 10.9-53-fold with respect to control. Substitution of hydrogen by chlorine in position C-2 of the phenoxazine ring increases the ability to enhance the uptake of VLB in KBCh(R)-8-5 cells by 1.15-19.7-fold. The effect of compounds 3, 5, 6, 12 and 17-21 on the efflux of VLB from KBCh(R)-8-5 cells has been examined and the results show that these compounds except 21 significantly inhibit the efflux of VLB consistent with being competitors for P-glycoprotein. Efflux of VLB from Rh30 cells in the presence of 100 muM of 1, 5, 12, 17, 20 and 21 result in 43-65% of the accumulated VLB being retained at 2 hr, suggesting that the phenoxazines have relatively little effect on VLB efflux from Rh30 cells. The previous work using DiOC(3) (3) has shown that the dye is a part of P-glycoprotein-mediated MDR phenotype. The KBCh(R)-8-5 cells are loaded with 360 nM of DiOC(3) (3) and efflux experiments are done in the absence or presence of 6, 12, or 21 by monitoring the fluorescence signal with time and the results in almost no efflux of the dye from the cells. These efflux data in KBCh(R)-8-5 and Rh30 cells suggest that 2-chlorophenoxazines may act through both P-glycoprotein mediated and independent mechanisms. Cytotoxicity has been determined and the IC50 values lie in the range 3.2-42.1 muM for N-10-chloropropyl, 2.7-16.7 muM for N-10-chlorobutyl and 51.6-68.6 muM for N-10-chloroacetyl derivatives against KBCh(R)-8-5 cells suggesting that the antiproliferative activity decreases in the order: - butyl > - propyl > - acetyl analogues. Further, substitution of hydrogen by chlorine in C-2 of phenoxazine ring causes a greater enhancement in the antiproliferative potency by 1.1-2.6-fold for KBCh(R)-8-5 cells than their respective counterparts, presumably due to increased hydrophobicity. Compounds at IC, have been evaluated for their efficacy to modulate the cytotoxicity of VLB in KBCh(R)-8-5 cells and compound 6 exhibits the greatest MDR reversal effect (136-fold) followed by compounds 12, 10, 13, 11 and so on. The structural features for reversal of MDR seem to include a hydrophobic phenoxazine ring with a -Cl group in the C-2 position and a tertiary amino group at a distance of three or four carbon chain from the tricyclic ring. Examination of the relationship between partition coefficient and cytotoxicity or anti-MDR activity shows no correlation suggesting that lipophilicity is not the sole determinant of potency for biological activity

Spectral and cyclic voltammetric investigation of oxidized products of 10-4 `-(N-diethylamino)butyl]-2-chlorophenoxazine and its applications in redox titrimetry

10-4'-(N-diethylamino)butyl]-2-chlorophenoxazine (DBCP) undergoes a reversible one-electron oxidation with cerium (IV) to form a pink coloured radical cation DBCP+.] in the presence of stoichiometric amounts DBCP: Ce(IV)= 1:1] of the reactants. The radical cation underwent a second one-electron oxidation to form a brownish yellow coloured dication DBCP2+] in the presence of more than one equivalent of cerium(IV), which was characterized by UV-vis, IR and mass spectrometry. The cyclic voltammogram of DBCP exhibited two anodic waves at 721 mV and 1158 mV and two cathodic waves at 653 mV and 1076 mV at a scan rate of 24 mV/s. The peak at 721 mV corresponds to the oxidation of DBCP to the radical cation DBCP+.] and the second anodic peak at 1158 mV stands for the oxidation of the radical cation to the dication DBCP2+]. Bromine oxidizes DBCP to three products as evidenced by HPLC and the tentatively predicted structures based on the mass-spectral data support the formation of brominated oxidized products. In order to explore the analytical applications, the optimum conditions for the successful use of DBCP as a redox indicator in the macro and micro estimation of ascorbic acid, methionine, isoniazid, phenylhydrazine hydrochloride and biotin using chloramine-B as oxidant, have been developed. The indicator gives sharp and stoichiometric end-points

Hydrophobic interactions of phenoxazine MDR modulators with bovine serum albumin

The binding of 10-3'-(N-piperidino)propyl]-2-trifluoromethy]phenoxazine 1, 10- 3'-(beta -hydroxyethylpiperazino)propyl]-2-trifluoromethylphenoxazine 2, 10-4'-(N-diethylamino)butyl]-2-trifluoromethylphenoxazine 3, 10-4'-(N-piperidino)butyl]-2-trifluoromethylphenoxazine 4 and 10-4'-(N-diethylamino)butyl]-2-chlorophenoxazine 5 to bovine serum albumin (BSA) has been measured by gel filtration and equilibrium dialysis methods. The binding of these modulators to albumin has been characterized by the following parameters: percentage of bound drug (beta), the association constant (K-I), the apparent binding constant (k) and the free energy (DeltaF degrees). In addition, the displacing activity of hydroxyzine and acetylsalicylic acid on the binding of phenoxazine to albumin has been examined. The binding of phenoxazine derivatives to serum transporter protein, BSA, is correlated with their partition coefficients. The results of the displacing experiments reveal that the phenoxazine benzene rings and the tertiary amines attached to the side chain of the phenoxazine moiety are bound to a hydrophobic area on the albumin molecule

Structural Studies of Some Phenoxazine Derivatives

The compound 10-3'-chlorobutyl phenoxazine (A), crystallizes in the triclinic space group P (I) over bar with a = 11.664(2)angstrom, b = 12.6292(2)angstrom, c = 10.5832(14)angstrom, alpha = 113.041(9)degrees, beta = 99.543(11)degrees, gamma = 83.340(10)degrees, V = 1412.5(3)angstrom(3) and Z = 2. The structure is refined to R = 0.102. There are two molecules in the asymmetric unit. The packing of the molecules shows stacking along all the three axes. When viewed down, b, the two molecules of the asymmetric unit appear almost perpendicular to each other. The compound, 10-(3'-N-Pyrrolidinopropyl)-2-trifluoro methyl phenoxazine hydrochloride (B), crystallizes in the monoclinic space group C2/c with a = 25.046(13)angstrom, b = 11.638(6)angstrom, c = 14.384(28 angstrom), beta = 107.25(8)degrees, V = 4003(2)angstrom(3) and Z = 8. The structure is refined to R = 0.065. the packing of the molecules shows stacking when viewed down b axis. The compound, 10-(N-morpholinoacetyl)-2-trifluoromethyl phenoxazine.(C), crystallizes in the monoclinic space group P2(1)/n with a = 12.710(4)angstrom, b = 8.5163(14)angstrom, c = 17.157(4)angstrom, beta = 108.62(2)degrees, V = 1759.9(7)angstrom(3) and Z = 4. The structure is refined to R = 0.041. The Packing of the molecules shows layered arrangement when viewed along b. The compound, 10-(N-chloroacetyl)-2-trifluoromethyl phenoxazine (D), crystallizes in the monoclinic space group P2(1)/a with a = 8.888(2)angstrom, b = 10.870(1)angstrom, c = 14.544(2)angstrom, beta = 102.48(2)degrees, V = 1372(4)angstrom(3) and Z = 2. The structure is refined to R = 0.089. Intra and intermolecular hydrogen bonds are observed in the structure. The compound, 10-N-piperidino acetyl phenoxazine (E), crystallizes in the monoclinic space group P2(1)/a with a - 12.314(4)angstrom, b = 9.108(3)angstrom, c = 14.586(4)angstrom, beta = 106.26(2)degrees, V = 1621.4(8)angstrom(3) and Z = 4. The structure is refined to R = 0.08. Packing of molecules shows stacking in two layers when viewed along b. One layer has the three fused rings and other layer has the cyclohexane ring

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Not AvailableThe aim of this study was to determine the effects of early-life bovine lactoferrin and host specific probiotic interventions on growth performance, mortality, and concentrations of immunoglobulin A and immunoglobulin G and transforming growth factor beta 1 (a marker of intestinal integrity) in serum of neonatal piglets. A total of eight piglet litters from parity matched sows were randomly divided into four groups and assigned to one of the four interventions: control (sterile normal saline), bovine lactoferrin (100 mg bovine lactoferrin), probiotic (1 × 109 colony forming unit (cfu) of swine origin Pediococcus acidilactici FT28 probiotic), and bovine lactoferrin + probiotic (100 mg bovine lactoferrin and 1 × 109 CFU of P. acidilactici FT28 probiotic). All the interventions were given once daily through oral route for first 7 days of life. The average daily gain (p = 0.0004) and weaning weight (p < 0.0001) were significantly improved in the probiotic group. The piglet survivability was significantly higher in bovine lactoferrin and probiotic groups than control group in Log-rank (Mantel-Cox) test. The concentrations of immunoglobulin A on day 21 in bovine lactoferrin, probiotic, and bovine lactoferrin + probiotic groups increased significantly (p < 0.05). Immunoglobulin G concentrations on day 7 and 15 in bovine lactoferrin and bovine lactoferrin + probiotic groups and on day 15 in probiotic group were significantly (p < 0.05) elevated, whereas, the concentration of transforming growth factor-β1 was significantly (p < 0.05) increased from day 7 to 21 in all the supplemented groups. In conclusion, the early-life bovine lactoferrin and P. acidilactici FT28 probiotic interventions reduced the mortality in the suckling piglets by promoting the systemic immunity and enhancing the intestinal integrity.Not Availabl