1,3,6-Trimethylpyrano[4,3-b]pyrrol-4(1H)-one

All the non-H atoms of the title compound, C10H11NO2, are almost coplanar [maximum deviation = 0.040 (3) angstrom]. The crystal structure is stabilized by C-H center dot center dot center dot O hydrogen bonds.

2-Chloro-8-methyl-3-[(pyrimidin-4-yloxy)methyl]quinoline

In the title compound, C15H12ClN3O, the quinoline ring system is essentially planar, with a maximum deviation of 0.017 (1) angstrom. The crystal packing is stabilized by pi-pi stacking interactions between the quinoline rings of adjacent molecule, with a centroid-centroid distance of 3.5913 (8) angstrom. Aweak C-H center dot center dot center dot pi contact is also observed between molecules.

5-(4-Chlorophenyl)-3-(2,4-dimethylthiazol-5-yl)-1,2,4-triazolo[3,4-a]isoquinoline

In the title molecule, C21H15ClN4S, the triazoloisoquinoline ring system is approximately planar, with an r.m.s. deviation of 0.054 (2) angstrom and a maximum deviation of 0.098 (2) angstrom from the mean plane for the triazole ring C atom that is bonded to the thiazole ring. The thiazole and benzene rings are twisted by 66.36 (7) and 56.32 (7)degrees respectively, with respect to the mean plane of the triazoloisoquinoline ring system. In the crystal structure, molecules are linked by intermolecular C-H center dot center dot center dot N interactions along the a axis. The molecular conformation is stabilized by a weak intramolecular pi-pi interaction involving the thiazole and benzene rings, with a centroid-centroid distance of 3.6546 (11) angstrom . In addition, two other intermolecular pi-pi stacking interactions are observed, between the triazole and benzene rings and between the dihydropyridine and benzene rings [centroid-centroid distances = 3.6489 (11) and 3.5967 (10) angstrom, respectively].

Molecular Basis for the Role of Staphylococcus aureus Penicillin Binding Protein 4 in Antimicrobial Resistance

Penicillin binding proteins (PBPs) are membrane-associated proteins that catalyze the final step of murein biosynthesis. These proteins function as either transpeptidases or carboxypeptidases and in a few cases demonstrate transglycosylase activity. Both transpeptidase and carboxypeptidase activities of PBPs occur at the D-Ala-D-Ala terminus of a murein precursor containing a disaccharide pentapeptide comprising N-acetyl-glucosamine and N-acetyl-muramic acid-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala. beta-Lactam antibiotics inhibit these enzymes by competing with the pentapeptide precursor for binding to the active site of the enzyme. Here we describe the crystal structure, biochemical characteristics, and expression profile of PBP4, a low-molecular-mass PBP from Staphylococcus aureus strain COL. The crystal structures of PBP4-antibiotic complexes reported here were determined by molecular replacement, using the atomic coordinates deposited by the New York Structural Genomics Consortium. While the pbp4 gene is not essential for the viability of S. aureus, the knockout phenotype of this gene is characterized by a marked reduction in cross-linked muropeptide and increased vancomycin resistance. Unlike other PBPs, we note that expression of PBP4 was not substantially altered under different experimental conditions, nor did it change across representative hospital- or community-associated strains of S. aureus that were examined. In vitro data on purified recombinant S. aureus PBP4 suggest that it is a beta-lactamase and is not trapped as an acyl intermediate with beta-lactam antibiotics. Put together, the expression analysis and biochemical features of PBP4 provide a framework for understanding the function of this protein in S. aureus and its role in antimicrobial resistance.

Synthesis and identification of a new class of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzo[d]thiazole derivatives as potent antileukemic agents

Benzothiazoles are multitarget agents with broad spectrum of biological activity. Among the antitumor agents discovered in recent years, the identification of various 2-(4-aminophenyl) benzothiazoles as potent and selective antitumor drugs against different cancer cell lines has stimulated remarkable interest. Some of the benzothiazoles are known to induce cell cycle arrest, activation of caspases and interaction with DNA molecule. Based on these interesting properties of benzothiazoles and to obtain new biologically active agents, a series of novel 4,5,6,7-tetrahydrobenzo[d]thiazole derivatives 5(a-i) were synthesized and evaluated for their efficacy as antileukemic agents in human leukemia cells (K562 and Reh). The chemical structures of the synthesized compounds were confirmed by H-1 NMR, LCMS and IR analysis. The cytotoxicity of these compounds were determined using trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Results showed that, these compounds mediate a significant cytotoxic response to cancer cell lines tested. We found that the compounds having electron withdrawing groups at different positions of the phenyl ring of the thiourea moiety displayed significant cytotoxic effect with IC50 value less than 60 mu M. To rationalize the role of electron withdrawing group in the induction of cytotoxicity, we have chosen molecule 5g (IC50 similar to 15 mu M) which is having chloro substitution at ortho and para positions. Flow cytometric analysis of annexin V-FITC/ propidium iodide (PI) double staining and DNA fragmentation suggest that 5g can induce apoptosis.

ErbB-2 expression and its association with other biological parameters of breast cancer among Indian women

Overexpression of the epidermal growth factor receptor family genes, which include ErbB-1, 2, 3 and 4, has been implicated in a number of cancers. We have studied the extent of ErbB-2 overexpression among Indian women with sporadic breast cancer. Methods: Immmunohistochemistry and genomic polymerase chain reaction (PCR) were used to study the ErbB2 overexpression. ErbB2 status was correlated with other clinico-pathological parameters, including patient survival. Results: ErbB-2 overexpression was detected in 43.2% (159/368) of the cases by immunohistochemistry. For a sub-set of patients (n = 55) for whom total DNA was available, ErbB-2 gene amplification was detected in 25.5% (14/55) of the cases by genomic PCR. While the ErbB2 overexpression was significantly higher in patients with lymphnode (χ2 = 12.06, P≤ 0.001), larger tumor size (χ2 = 8.22, P = 0.042) and ductal carcinoma (χ2 = 15.42, P ≤ 0.001), it was lower in patients with disease-free survival (χ2 = 22.13, P ≤ 0.001). Survival analysis on a sub-set of patients for whom survival data were available (n = 179) revealed that ErbB-2 status (χ2 =25.94, P ≤ 0.001), lymphnode status (χ2 = 12.68, P ≤ 0.001), distant metastasis (χ2 = 19.49, P ≤ 0.001) and stage of the disease (χ2 = 28.04, P ≤0.001) were markers of poor prognosis. Conclusions: ErbB-2 overexpression was significantly greater compared with the Western literature, but comparable to other Indian studies. Significant correlation was found between ErbB-2 status and lymphnode status, tumor size and ductal carcinoma. ErbB-2 status, lymph node status, distant metastasis and stage of the disease were found to be prognostic indicators.

Investigations of superconducting bismuth cuprates of the general formula Bi2-xPbx(Ca,Sr,Y)n 1 Cun O2n 4 δ

In the (Bi,Pb)-Sr-Cu-O system we have examined many compositions which are either metallic or semiconducting. In the Bi2-xPbx(Ca, Sr)n+1 Cun O2n+4+δ system, we have established the superconducting properties of the n = 1 to 4 members. The Tc increases from n = 1 to 3 and does not increase further when n = 4. In Bi2Ca1-x,YxSr2Cu2Oy, the Tc decreases with increase in x.

Syntheses based on cyclohexadienes. Part 2. Convenient synthesis of 6-alkylsalicylates, 6-alkyl 2,4-dihydroxybenzoate, and 2,5-dialkylresorcinols

A one pot synthesis of 6-alkylsalicylates and 6-alkyl-2,4- dihydroxybenzoates is described. Cycloaddition of 1-methoxycyclohexa-1,4- or 1,3-dienes with alkylpropiolic esters results in the regio-specific formation of 2-alkyl-6-methoxybenzoates. Thus, methyl 2-methoxy-6-methyl benzoate, methyl 2,4-dimethoxy-6-methylbenzoate, methyl 2,5-dimethoxy-6-methylbenzoate, methyl 2-methoxy-4,6-dimethylbenzoate, and ethyl 2-butyl-4,6-dimethoxybenzoate, have been prepared. By making use of this method, the synthesis of two dihydroisocoumarins namely (±)-mellein (12) and (±)-6-methoxy- mellein (14) is described. Employing a similar strategy, a novel route to 2,5-dialkylresorcinols has been developed. Stemphol (24b) and the antibiotic DB2073 (24d) have been synthesized.

2,4-Dichloro-7,8-dimethylquinoline

There are two independent molecules in the asymmetric unit of the title compound, C11H9Cl2N, both of which are essentially planar [maximum deviations of 0.072 (5) and 0.072 (7) angstrom]. In the crystal structure, weak pi-pi stacking interactions [centroid-centroid distances = 3.791 (3) angstrom and 3.855 (3) angstrom] link pairs of molecules.

3-[(2-Chloro-6-methylquinolin-3-yl)methyl]quinazolin-4(3H)-one

In the title molecule, C19H14ClN3O, the quinoline and quinazoline ring systems form a dihedral angle of 80.75 (4)degrees. In the crystal, the molecules are linked by pairs of C-H center dot center dot center dot N hydrogen bonds into centrosymmetric dimers, generating R-2(2)(6) ring motifs. The structure is further stabilized by C-H center dot center dot center dot pi interactions and pi-pi stacking interactions [centroid-centroid distances = 3.7869 (8) and 3.8490 (8) angstrom].

Extending lagrange interpolation to develop a 4-node quadrilateral element

Today finite element method is a well established tool in engineering analysis and design. Though there axe many two and three dimensional finite elements available, it is rare that a single element performs satisfactorily in majority of practical problems. The present work deals with the development of 4-node quadrilateral element using extended Lagrange interpolation functions. The classical univariate Lagrange interpolation is well developed for 1-D and is used for obtaining shape functions. We propose a new approach to extend the Lagrange interpolation to several variables. When variables axe more than one the method also gives the set of feasible bubble functions. We use the two to generate shape function for the 4-node arbitrary quadrilateral. It will require the incorporation of the condition of rigid body motion, constant strain and Navier equation by imposing necessary constraints. The procedure obviates the need for isoparametric transformation since interpolation functions are generated for arbitrary quadrilateral shapes. While generating the element stiffness matrix, integration can be carried out to the accuracy desired by dividing the quadrilateral into triangles. To validate the performance of the element which we call EXLQUAD4, we conduct several pathological tests available in the literature. EXLQUAD4 predicts both stresses and displacements accurately at every point in the element in all the constant stress fields. In tests involving higher order stress fields the element is assured to converge in the limit of discretisation. A method thus becomes available to generate shape functions directly for arbitrary quadrilateral. The method is applicable also for hexahedra. The approach should find use for development of finite elements for use with other field equations also.

4,4′-Bipyridyl complexes of iron: Magnetic, Mössbauer and other spectroscopic studies

4,4prime-Bipyridyl (4,4prime-bipy) complexes of ferrous salts of the Fe(4,4prime-bipy)x(anion)y type (where x or y=1 or 2) and of ferric salts of the Fe(4,4prime-bipy)m(anion)n type (where m=1 or 2 and n=3) have been synthesised. Elemental analyses, i.r. and electronic spectra, magnetic and Mössbauer studies have been performed to characterize the complexes. 4,4prime-Bipy and some anions are inferred to act as bridging ligands. The magnetic moments, electronic and Mössbauer spectra suggest that the complexes are of high spin type with distorted octahedral structures. The value of the isomer shift and quadrupole splitting are discussed in terms of bonding of the ligand and anions.

Open manifolds, Ozsvath-Szabo invariants and exotic R-4 ` S

We construct an invariant of certain open four-manifolds using the Heegaard Floer theory of Ozsvath and Szabo. We show that there is a manifold X homeomorphic to R-4 for which the invariant is non-trivial,showing that X is an exotic R-4. This is the first invariant that detects exotic R-4' s. (C) 2009 Published by Elsevier GmbH.