Molecular docking, spectroscopic, and quantum chemical studies on aromatic heterocycle tetrakis(4-pyridyl)cyclobutane regioisomers: potential membrane-permeable inhibitors.

Aromatic heterocyclic compounds are commonly used in pharmaceutical and agrochemical products. The usage has been also extended in the production of corrosion inhibitors and electronic, opto-electronic, and NLO devices. The four regioisomers of the aromatic heterocyclic molecule, tetrakis(4-pyridyl)cyclobutane (tpcb), were optimized, and their chemical, electronic, and biological properties were examined. The rctt and rtct isomers were isolated and further characterized by the infrared and Raman spectroscopic techniques, and their vibrational modes with attention on important functional groups were discussed. The theoretical vibrational data obtained by DFT/B3LYP/6-311++G(d,p) were in very good agreement with the experimental ones. The occupancy, bond polarization, hybridization of the N-C bond, bonding characteristics between the pyridyl carbon and cyclobutane moiety, and distribution of electron density for the four tpcb isomers have been explored through NBO analysis. The inversion barrier of the cyclobutane moiety was obtained based on the optimized structures of the planar and puckered configurations of the isomers. The rccc isomer exhibited the least electrophilic character compared to the other tpcb isomers. The chemical significance of tpcb has been further explained by the wave function analyses. Molecular docking results revealed that the tpcb ligand would possess a potential anti-viral and anti-bacterial activity via a membrane-permeable mechanism.

Spectral characterization, thermochemical studies, periodic SAPT calculations and detailed quantum mechanical profiling various physico-chemical properties of 3,4-dichlorodiuron.

A set of experimental and computational techniques have been applied for the understanding of fundamental spectroscopic and reactive properties of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron) compound. Experimental techniques employed in this study encompassed spectroscopic characterization via IR and Raman approaches, while optical properties were studied by measurements of UV/Vis spectra. The thermogravimetric analysis was also studied in order to analyze the stability of diuron. Aside from the determination of reactive properties, DFT calculations on isolated molecules were also used to thoroughly visualize and analyze spectroscopic properties such as IR and UV/Vis. MD simulations were used in order to understand interactions with water, while periodic DFT calculations were used in order to analyze band structure and density of states of the diuron crystal structure. Since the crystal structure of diuron is known, it was used in order to extract the relevant molecular pairs and investigate interactions between them by DFT and symmetry adapted perturbation theory approaches (SAPT).

Conformational profile, vibrational assignments, NLO properties and molecular docking of biologically active herbicide1,1-dimethyl-3-phenylurea.

1,1-Dimethyl-3-phenylurea (known as fenuron) which is a phenyl urea-based widely used herbicide exhibits interesting structural and conformational properties and a notable biological activity. A detailed analysis on the vibrational, molecular and electronic characteristics of fenuron has been carried out. Potential energy scans (PESs) performed at the B3LYP/6-311++G(d,p) level of theory predicted two possible minima corresponding to the optimized anti and synforms resulting from the internal rotation about the N-C bond. The presence of an auxochrome together with the interaction with DMSO solvent exhibited a blue shift corresponding to the C=O orbitals. Delocalization of HOMO and LUMO orbital facilitated the charge transfer effect in the molecule. The calculated HOMO-LUMO energies, chemical potential, energy gap and global hardness suggested a low softness value for the compound while its biological activity was described by the value of electrophilicity. Chlorine substitution in the phenyl ring influenced the orbital delocalization for ortho and para substitutions but that of meta remained unaffected. NLO properties were noticed to increase due to chlorine substitution in the parent molecule. The docking results suggested that the compound exhibits an inhibitory activity against mitochondrial ubiquinol-cytochrome-c reductase and can be developed as a potential anticancer agent.

Major and trace element evaluation of the campano-maastrichtian sediments of anambra basin exposed around Enugu, Nigeria

ABSTRACT: An integrated geochemical and sedimentological study of the Campano- Maastrichtian sediment of Ajali and Owelli Formation exposed within the southern portion of the Anambra basin was undertaken to determine the sandstone provenance, tectonic setting, and paleo-weathering conditions. All sandstone samples are enriched in quartz (Q) but poor in feldspar (F) andlithic-fragments (L). The major-element concentrations of these sandstones reveal the relative homogeneity of their source. Geochemically, the sandstones are classified as quartzarenite, sub-litharenite, and subarkose. Tectonic setting discrimination diagrams suggest a passive continental margin. The sediments are enriched in SiO2 and depleted in Na2O, CaO and TiO2.Chemical index of weathering (CIW) of the sample suggests intense recycling and high degree of weathering in a humid climatic condition. Results of the elemental ratios critical of provenance compared to those of felsic and basic derived sediment of UCC and PAAS values suggests a felsic source rock. Cu/Zn, U/Th, Ni/Co and (Cu+Mo)/Zn paleo-oxygenation ratios used as redox parameters depicts an oxic environment. Finally, presence of minerals, like Anatase, Rutile and Microcline depicts an igneous and metamorphic source terrain

A case of a Japanese neonate with congenital ichthyosiform erythroderma diagnosed as Netherton syndrome.

We report a 6-day-old Japanese girl showing generalized erythroderma accompanied by yellowish, exfoliative scaling that was accentuated on the face and scalp. Histological analysis showed psoriasiform dermatitis with acanthotic epidermis and premature shedding of the stratum corneum. Measurement of trypsin-like hydrolytic activity in SC showed six-fold greater activity compared with age-matched controls. DNA analysis revealed two mutations, 375delAT and 966insC, in exons 5 and 11, respectively, of the SPINK5 gene. Although at 4 weeks the child was still too young to display characteristic hair abnormalities or atopic diathesis, we diagnosed Netherton syndrome based on enzyme assay and DNA analysis.

Evaluation of Jatropha curcas latex ointment formulations in-vitro and in-vivo

The dried latex of Jatropha curcas was formulated into ointments of 2.5; 5 and 10 w/w concentrations in hydrocarbon base B.P.C; using the fusion and levigation methods. The efficacy of the ointments was evaluated in-vitro using the agar diffusion method and cup-plate technique with the following organisms: Escherichia coli (N.C.T.C. 10418); Staphylococcus aureus (N.C.T.C. 6571); Microsporum sp.; Epidermophyton sp. and Trichophyton sp.; which were clinical isolates. For the in-vivo studies; volunteers with Tinea capitis from a primary school were used. The results indicated that the ointment formulations were active both in-vitro and in-vivo. The activities of the test formulations compared favorably with those from the standard formulations; i.e. Whitfield's ointment B.P. and penicillin ointment B.P.C. The results also indicated that the stability of latex was maintained within the ointment base over the nine months period of storage

[Intrasellar epidermoid cyst].

We report a rare case of intrasellar epidermoid cyst. A 61-year-old man presented with complaints of the disturbance of consciousness and general fatigability. His laboratory data showed panhypopituitarism and MRI revealed the cystic tumor located at the intrasellar region. Tumor was removed by transsphenoidal approach and histological examination of the surgical specimen showed that the cyst wall was composed of the stratified squamous epithelium with keratohyaline granules.

Subconjunctival immunization of mice for inducing IgE antibody response in parotic lymph node.

Subconjunctival immunization of mice with dinitrophenyl (DNP)-Ascaris plus alum led to the induction of a local anti-DNP IgE response in 8 days. Anti-DNP IgE was found to be secreted from isolated lymphocytes in the parotic lymph node neighboring the immunization site but not from those in the spleen and the mesenteric lymph node. The IgE response was also confirmed by the detection of C epsilon transcript in the parotic lymph node cells. Ocular topical application of betamethazone resulted in considerable suppression of the IgE response in the parotic lymph node, thus suggesting that this immunization protocol is useful for evaluating ocular topical anti-allergic drugs that are expected to suppress local IgE responses.

The secondary antigen-specific IgE response in murine lymphocytes is resistant to blockade by anti-IL4 antibody and an antisense oligodeoxynucleotide for IL4 mRNA.

In order to investigate the role of interleukin 4 (IL4) in the induction of antigen-specific IgE responses, we established culture conditions which allow the induction of anti-trinitrophenyl(TNP) IgE response by the coculture of TNP-keyhole limpet hemocyanin-primed C3H B cells with conalbumin (CA)-specific type 2 helper T (Th2) cell clone, D10.G4.1 in the presence of TNP-CA. A maximum level of anti-TNP IgE was secreted at 1 microgram/ml TNP-CA. By using filter-separated double-chamber culture plates, the physical contact between T cells and B cells was shown to be necessary in this response. Anti-TNP IgE synthesis was not significantly suppressed in the presence of 20-40 micrograms/ml monoclonal anti-IL4 (11B11), nor was the response further enhanced by the addition of recombinant IL4. 11B11 added together with anti-IL5 had also no suppressive effects on the IgE response. This apparent independence on IL4 might be due to the fact that IL4 is transferred from T cells to B cells in a transsynaptical way that would be refractory to the neutralization by 11B11. In order to test this possibility, we synthesized the phosphorothioate analogue of an antisense oligodeoxynucleotide against IL4 mRNA (S-oligo) for inhibiting IL4 production from Th2 cells specifically. S-oligo was effective at 10-20 micrograms/ml in suppressing IL4 production from D10.G4.1 cells by 80-90%. It was demonstrated that S-oligo, either alone or in combination with 11B11, did not significantly suppress anti-TNP IgE response. These results suggest that antigen-specific IgE response in primed B cells does not depend on IL4, but requires cognate interaction with Th2 cells.

Antigen-specific but not polyclonal IgE response in murine B cells cocultured with Th2 clone is refractory to suppression by IL4-depletion.

We established culture conditions allowing the induction of antitrinitrophenyl (TNP) IgE response by the coculture of unprimed C3H B cells with conalbumin (CA)-specific type 2 helper T cell clone, D10.G4.1 in the presence of TNP-CA. With the help of this culture system, the role of Th2 cells and interleukin 4 (IL4) derived from them in the induction of antigen-specific IgE response was analyzed. A maximum level of anti-TNP IgE was secreted at 0.5-1 micrograms/ml TNP-CA. When the antigen was increased to 100 micrograms/ml, anti-TNP IgE production was abolished, while antigen-nonspecific (polyclonal) IgE was produced concomitantly. Anti-TNP IgE synthesis was not significantly suppressed in the presence of monoclonal anti-IL4 (11B11), nor was the response further enhanced by the addition of recombinant IL4. In contrast, polyclonal IgE response was abolished by 11B11. In order to deplete endogenous IL4 more strictly, we employed an antisense DNA for IL4 mRNA that can effectively inhibit IL4 production from D10 cells. Even in the presence of both 11B11 and the antisense DNA, it was found that anti-TNP IgE response was not suppressed significantly. These results suggest that antigen-specific IgE response induced in B cells cocultured with established Th2 cells does not depend on IL4 in contrast to polyclonal IgE response.

Suppression of interleukin 4 production from type 2 helper T cell clone by antisense oligodeoxynucleotide.

Type 2 helper T cell (Th2) clone has been reported to secrete interleukin (IL) 4 and IL5 in response to the specific antigen presented by syngeneic antigen-presenting cells. In the present report, we synthesized phosphorothioate analogue of an antisense oligodeoxynucleotide complementary to nucleotide 17-36 of IL4 mRNA (S-oligo), and tested its ability to inhibit IL4 production from a Th2 clone, D10.G4.1. (D10). D10 cells were cultured with mitomycin C-treated C3H spleen cells in the presence of 100 micrograms/ml conalbumin for 48-72 h. Secreted IL4 and IL5 were assayed biologically using HT2 cells and dextran sulfate-stimulated murine B cells, respectively. When 5-10 micrograms/ml S-oligo was added to the culture, IL4 production from D10 was suppressed by 70-90%. The same concentrations of S-oligo inhibited neither the antigen-induced proliferation of D10 nor the secretion of IL5 from the Th2 clone. These results suggest that this S-oligo is useful for inhibiting the production of IL4 preferentially without affecting other functions of Th2 cells.

In vitro antigen-specific IgE response is refractory to suppression by interferon-gamma.

Although interferon (IFN)-gamma has been shown to be involved in the down-regulation of polyclonal IgE response in murine B cells that were activated by lipopolysaccharide (LPS) and interleukin 4 (IL4), effects of IFN-gamma on antigen-specific IgE responses have not been fully investigated. We have developed the following culture systems for inducing antigen-specific IgE responses in murine lymphocytes, and examined the effects of IFN-gamma on the following responses in vitro. (1) Anti-trinitrophenyl (TNP) IgE response induced by the stimulation with TNP-keyhole limpet hemocyanin (KLH) of BALB/c spleen cells that had been primed in vivo with the same antigen. (2) Anti-TNP IgE response induced by the coculture of unprimed C3H B cells with conalbumin (CA)-specific helper T cell clone, D10.G4.1, in the presence of TNP-CA. The former anti-TNP IgE response was not suppressed, and the latter suppressed only partially (less than 30%) by the addition of 100-200 U/ml IFN-gamma. In contrast, polyclonal IgE response in murine B cells that were stimulated by LPS and IL4 was abolished by 10 U/ml IFN-gamma. These results indicate that IgE production from antigen-stimulated B cells, in contrast to those activated polyclonally, are refractory to direct suppression by IFN-gamma.