Halogen Bonding and Structural Modularity in 2,3,4-and 3,4,5-Trichlorophenol

The crystal structure of 3,4,5-trichlorophenol contains hydrogen bonded domains that occur respectively in the structures of 4-chlorophenol and 3,5-dichlorophenol. Such modularity is also seen in 2,3,4-trichlorophenol. These structures, and those of the six isomeric dichlorophenols, illustrate the importance of halogen bonding as a structure determining interaction.

N-(2-Amino-3,5-dibromobenzyl)-N-methylcyclohexan-1-aminium p-toluenesulfonate

The title compound, C(14)H(21)Br(2)N(2)(+)center dot C(7)H(7)O(3)S, features a salt of protonated bromhexine, a pharmaceutical used in the treatment of respiratory disorders, and the p-toluenesulfonate anion. The crystal packing is stabilized by intermolecular N-H center dot center dot center dot O, N-H center dot center dot center dot Br and C-H center dot center dot center dot O hydrogen bonds.

(2E)-1-(5-Chlorothiophen-2-yl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one

In the title molecule, C(16)H(15)ClO(4)S, the chlorothiophene and trimethoxyphenyl rings make a dihedral angle of 31.12 (5)degrees. The C = C double bond exhibits an E conformation. In the crystal, C-H center dot center dot center dot O interactions generate bifurcated bonds, linking the molecules into chains along the b axis.

3-Ethyl-4-methyl-1H-pyrazol-2-ium-5-olate

The title compound, C(6)H(10)N(2)O, is a zwitterionic pyrazole derivative. The crystal packing is predominantly governed by a three-center iminium-amine N(+)-H center dot center dot center dot O(-)center dot center dot center dot H-N interaction, leading to an undulating sheet-like structure lying parallel to (100).

Ethyl 6-methyl-2-sulfanylidene-4-[4(trifluoromethyl)phenyl]-1,2,3,4-tetrahyd ropyrimidine-5-carboxylate

The title compound, C(15)H(15)F(3)N(2)O(2)S, adopts a conformation with an intramolecular C-H center dot center dot center dot pi interaction. The dihedral angles between the planes of the 4-(trifluoromethyl) phenyl and ester groups with the plane of the six-membered tetrahydropyrimidine ring are 81.8 (1) and 16.0 (1)degrees, respectively. In the crystal structure, intermolecular N-H center dot center dot center dot S hydrogen bonds link pairs of molecules into dimers and N-H center dot center dot center dot O interactions generate hydrogen-bonded molecular chains along the crystallographic a axis.

2-{[{2-Hydroxy-3-[2-methyl-5-(propan-2-yl)phenoxy]propyl}(pyridin -2-ylmethyl)amino]methyl}phenol

In the title racemic compound, C(26)H(32)N(2)O(3), an intramolecular O-H center dot center dot center dot N hydrogen bond is formed between the phenolic OH group and the tertiary amine N atom. Another O-H center dot center dot center dot N hydrogen bond that is formed between the OH group and the pyridine N atom links the molecules into a polymeric chain extending along the a axis. The structure is further stabilized by intramolecular and intermolecular C-H center dot center dot center dot O interactions.

(2E)-1-(5-Chlorothiophen-2-yl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one

In the title compound, C(15)H(13)ClO(3)S, the chlorothiophene and dimethoxyphenyl groups are linked by a prop-2-en-1-one group. The C=C double bond exhibits an E conformation. The molecule is non-planar, with a dihedral angle of 31.12 (5)degrees between the chlorothiophene and dimethoxyphenyl rings. The methoxy group at position 3 is coplanar with the benzene ring to which it is attached, with a C-O-C-C torsion angle of -3.8 (3)degrees. The methoxy group attached at position 2 of the benzene ring is in a (+)synclinal conformation, as indicated by the C-O-C-C torsion angle of -73.6 (2)degrees. In the crystal, two different C-H center dot center dot center dot O intermolecular interactions generate chains of molecules extending along the b axis.

An efficient one-pot synthesis and photoinduced DNA cleavage studies of 2-chloro-3-(5-aryl-4,5-dihydroisoxazol-3-yl)quinolines

4,5-Dihydroisoxazoles continue to attract considerable interest due to their wide spread biological activities. Here, we identify an efficient protocol for the preparation of 4,5-dihydroisoxazoles (2-isaxazolines) (4a-g) from quinolinyl chalcones. The nucleolytic activities of synthesized compounds were investigated by agarose gel electrophoresis. All these compounds were showed the remarkable DNA cleavage activity (concentration dependent) with pUC19 DNA at 365 nm UV light. The DNA cleavage activity was significantly enhanced by the presence of iminyl and carboxy radicals of DIQ. (C) 2012 Elsevier Ltd. All rights reserved.

A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent.

A Novel Anticancer Agent, 8-Methoxypyrimido4 `,5 `: 4,5]thieno(2,3-b) Quinoline-4(3H)-One Induces Neuro 2a Neuroblastoma Cell Death through p53-Dependent, Caspase-Dependent and Independent Apoptotic Pathways

Neuroblastoma is the most common cancer in infants and fourth most common cancer in children. Despite recent advances in cancer treatments, the prognosis of stage-IV neuroblastoma patients continues to be dismal which warrant new pharmacotherapy. A novel tetracyclic condensed quinoline compound, 8-methoxypyrimido 4 `,5 `: 4,5] thieno(2,3-b) quinoline-4(3H)-one (MPTQ) is a structural analogue of an anticancer drug ellipticine and has been reported to posses anticancer property. Study on MPTQ on neuroblastoma cells is very limited and mechanisms related to its cytotoxicity on neuroblastoma cells are completely unknown. Here, we evaluated the anticancer property of MPTQ on mouse neuro 2a and human SH-SY5Y neuroblastoma cells and investigated the mechanisms underlying MPTQ-mediated neuro 2a cell death. MPTQ-mediated neuro 2a and SH-SY5Y cell deaths were found to be dose and time dependent. Moreover, MPTQ induced cell death reached approximately 99.8% and 90% in neuro 2a and SH-SY5Y cells respectively. Nuclear oligonucleosomal DNA fragmentation and Terminal dUTP Nick End Labelling assays indicated MPTQ-mediated neuro 2a cell death involved apoptosis. MPTQ-mediated apoptosis is associated with increased phosphorylation of p53 at Ser15 and Ser20 which correlates with the hyperphosphorylation of Ataxia-Telangiectasia mutated protein (ATM). Immunocytochemical analysis demonstrated the increased level of Bax protein in MPTQ treated neuro 2a cells. MPTQ-mediated apoptosis is also associated with increased activation of caspase-9, -3 and -7 but not caspase-2 and -8. Furthermore, increased level of caspase-3 and cleaved Poly ( ADP Ribose) polymerase were observed in the nucleus of MPTQ treated neuro 2a cells, suggesting the involvement of caspase-dependent intrinsic but not extrinsic apoptotic pathway. Increased nuclear translocation of apoptosis inducing factor suggests additional involvement of caspase-independent apoptosis pathway in MPTQ treated neuro 2a cells. Collectively, MPTQ-induced neuro 2a cell death is mediated by ATM and p53 activation, and Bax-mediated activation of caspase-dependent and caspase-independent mitochondrial apoptosis pathways.

Evolution of Nanocrystalline Ba2NaNb5O15 in 2BaO-0.5Na(2)O-2.5Nb(2)O(5)-4.5B(2)O(3) Glass System and Its Refractive Index and Band Gap Tunability

Monophasic Ba2NaNb5O15 was crystallized at nanometer scale (12-36 nm) in 2BaO-0.5Na(2)O-2.5Nb(2)O(5)- 4.5B(2)O(3) glass system. To begin with, optically transparent glasses, in this system, were fabricated via the conventional melt. quenching technique. The amorphous and glassy characteristics of the as-quenched samples were respectively confirmed by X-ray powder diffraction and differential thermal analyses. Nearly homogeneous distribution of Ba2NaNb5O15 (BNN) nanocrystals associated with tungsten bronze structure akin to their bulk parent structure was accomplished by subjecting the as-fabricated glasses to appropriate heat-treatment temperatures. Indeed transmission electron microscopy (TEM) carried out on these samples corroborated the presence of Ba2NaNb5O15 nanocrystals dispersed in a continuous glass matrix. The as-quenched glasses were similar to 75% transparent in the visible range of the electromagnetic spectrum. The optical band gap and refractive index were found to have crystallite size (at nanoscale) dependence. The optical band gap increased with the decrease in crystallite size. The refractive indices of the glass nanocrystal composites as determined by Brewster angle method were rationalized using different empirical models. The refractive index dispersion with wavelength of light was analyzed on the basis of the Sellmeier relations. At room temperature under UV excitation (355 nm) these glass nanocrystal composites displayed violet-blue emission which was ascribed to the defects states.

Frequency and Temperature-Independent Electrical Transport Properties of 2BaO-0.5Na(2)O-2.5Nb(2)O(5)-4.5B(2)O(3) Glass-Ceramics

The temperature (300-973K) and frequency (100Hz-10MHz) response of the dielectric and impedance characteristics of 2BaO-0.5Na(2)O-2.5Nb(2)O(5)-4.5B(2)O(3) glasses and glass nanocrystal composites were studied. The dielectric constant of the glass was found to be almost independent of frequency (100Hz-10MHz) and temperature (300-600K). The temperature coefficient of dielectric constant was 8 +/- 3ppm/K in the 300-600K temperature range. The relaxation and conduction phenomena were rationalized using modulus formalism and universal AC conductivity exponential power law, respectively. The observed relaxation behavior was found to be thermally activated. The complex impedance data were fitted using the least square method. Dispersion of Barium Sodium Niobate (BNN) phase at nanoscale in a glass matrix resulted in the formation of space charge around crystal-glass interface, leading to a high value of effective dielectric constant especially for the samples heat-treated at higher temperatures. The fabricated glass nanocrystal composites exhibited P versus E hysteresis loops at room temperature and the remnant polarization (P-r) increased with the increase in crystallite size.

DNA intercalative 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline induces cell cycle arrest and apoptosis in leukemia cells

DNA intercalators are one of the interesting groups in cancer chemotherapy. The development of novel anticancer small molecule has gained remarkable interest over the last decade. In this study, we synthesized and investigated the ability of a tetracyclic-condensed quinoline compound, 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline (BPTQ), to interact with double-stranded DNA and inhibit cancer cell proliferation. Circular dichroism, topological studies, molecular docking, absorbance, and fluorescence spectral titrations were employed to study the interaction of BPTQ with DNA. Cytotoxicity was studied by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Further, cell cycle analysis by flow cytometry, annexin V staining, mitochondrial membrane potential assay, DNA fragmentation, and western blot analysis were used to elucidate the mechanism of action of BPTQ at the cellular level. Spectral, topological, and docking studies confirmed that BPTQ is a typical intercalator of DNA. BPTQ induces dose-dependent inhibitory effect on the proliferation of cancer cells by arresting cells at S and G2/M phase. Further, BPTQ activates the mitochondria-mediated apoptosis pathway, as explicated by a decrease in mitochondrial membrane potential, increase in the Bax:Bcl-2 ratio, and activation of caspases. These results confirmed that BPTQ is a DNA intercalative anticancer molecule, which could aid in the development of future cancer therapeutic agents.

A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent. (c) 2011 Wiley Periodicals, Inc.