Design, synthesis and evaluation of novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety as antiangiogenic agents.

Novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety have been synthesized and screened for their antiangogenic activities, by testing their ability to inhibit human umbilical vein endothelial cell (HUVEC) proliferation, cord formation and migration in response to chemoattractant. 3 compounds 19, 23 and 26 showed antiangiogenic activities at non-cytotoxic concentrations. Compound 19 was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Compound 42 showed a significant cytotoxic effect on the tested cancer cell lines and less antiangiogenesis activity compared to compounds 19, 23 and 26. All the tested compounds, in contrary to TNP-470, interfered with the migratory function of HUVECs in response to vascular endothelial growth factor rather than the endothelial cells proliferation or cord formation. Moreover, a docked pose of compounds 19 and 26 was obtained bound to kinase insert domain receptor using Molecular Operating Environment module.

[Confocal microscopy in corneal dystrophies: a comparison between confocal slit scanning (ConfoScan P2) and laser scanning microscopy (Rostock Cornea Modul-HRT II)]. / Konfokale Scanning-Mikroskopie: Eine vergleichende Darstellung von Hornhautdystrophiebefunden mittels ConfoScanP2 und Rostock Cornea Modul-HRT II.

BACKGROUND: The object of this work was a comparison of confocal images of corneal dystrophies made by a slit scanning microscope versus a laser scanning microscope. MATERIAL AND METHODS: Using the Rostock Cornea Modul-HRT II as a confocal laser scanning microscope the images of five patients with some epithelial, stromal and endothelial corneal dystrophies were acquired. The pictures were compared qualitatively with those taken by the slit scanning microscope "ConfoScan P2" from corresponding pathologies. Also, the images of normal corneas of ten healthy persons were acquired for a qualitative comparison. RESULTS: Confocal images from both devices were able to provide significant helpful diagnostic findings about the corneal microstructure. Essential qualitative differences between the images of both devices used were not observed. Due to the additional hardware components and the software module for image acquisition, analysis and archiving, the RCM-HRT II is favoured over the "ConfoScan P2". Nevertheless, the evaluation in favour of the RCM-HRT II has to be confined because an optimised, user-friendly enhancement, the "ConfoScan 4" is currently available. CONCLUSION: Evaluating corneal dystrophies in vivo, an equivalent utility of both technical approaches has been observed.

Downmodulation of bFGF-binding protein expression following restoration of p53 function.

Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector-mediated wild-type p53 transduction results in growth inhibition of squamous cell carcinoma of the head and neck tumor cells both in vitro and in a xenograft mouse model. This growth inhibition is associated with the down-regulation of the expression of fibroblast growth factor binding protein, a secreted protein required for the activation of angiogenic factor basic FGF. These findings suggest that wtp53-induced tumor regression is due, at least in part, to antiangiogenesis mediated by the downmodulation of fibroblast growth factor binding protein.

Spectrophotometric determination of two N-(4-quinolyl) anthranilic acid derivative (glafenine and floctafenine).

Spectrophotometric methods were developed for the determination of glafenine and floctafenine. The first method depends upon the determination of glafenine in raw material and tablets as well as in the presence of its main degradation product glafenic acid (up to 40%). Differential first derivative spectral response at 245 nm in 0.1 N hydrochloric acid, where the corresponding degradation product exhibits no contribution in 0.1 N sodium hydroxide. The method allows the determination of 2.5-30 microg ml(-1). The second method depends upon the reaction of floctafenine with 2,3-dichloro 5,6-dicyano-p-benzoquinone (DDQ) in acetonitrile to give highly colored complex that could be measured quantitatively at (about) lambda(max) 538 nm. The method permits the determination of 40-180 microg ml(-1) or by measuring the first derivative spectral response of the color at 610 nm. The method permits the determination of floctafenine in presence of thiocolchicoside. The methods mentioned both simplicity and sensitivity, having excellent precision and accuracy (100.31 +/- 0.63, 100.78 +/- 0.77 and 99.90 +/- 0.56 for glafenine and floctafenine, respectively). The results were of comparable accuracy and reproducibility with the reported methods.

Spectrophotometric determination of loperamide hydrochloride by acid-dye and charge-transfer complexation methods in the presence of its degradation products.

Two simple, sensitive and accurate spectrophotometric methods for the determination of loperamide hydrochloride (lop. HCl) are described. The first method is based on the formation of ion-pair association complex (1:1) with bromothymol blue (BTB), bromophenol blue (BPB) and naphthol blue black B (NBB). The coloured products are extracted into chloroform, and measured spectrophotometrically at 414 (BTB), 415 (BPB) and 627 nm (NBB). Beer's law was obeyed in the ranges of 5-35, 5-30 and 0.8-11.2 microg ml(-1) for BTB, BPB and NBB methods, respectively. The method was found to be specific for the analysis of the drug in presence of its degradation products which can be detected by HPLC procedure. The second method is based on the reaction of the basic loperamide with iodine in chloroform to give molecular charge-transfer complex with intense bands at 295 and 363 nm. Beer's law was obeyed in the ranges 2.5-17.5 and 2.5-22.5 microg ml(-1) for the method at 295 and 363 nm, respectively. Optimization of the different experimental conditions are described for both methods. The proposed methods have been applied successfully for the analysis of the drug in pure form and in its dosage forms. The methods have the advantage of being highly sensitive and simple for the determination of a small dose drug, which is also a weak UV-absorbing compound.

[Confocal microscopy in corneal dystrophies]. / Konfokale Mikroskopie bei Hornhautdystrophien.

BACKGROUND: Confocal microscopy represents a methodology that allows in vivo examination of corneal morphology, particularly of the epithelium and stroma. MATERIAL AND METHODS: Using the confocal microscope "ConfoScan Modell P2" epithelial, stromal and endothelial changes were evaluated in 11 patients with corneal dystrophies. All findings were compared with data from healthy individuals. RESULTS: Confocal images could be correlated to conventional (slitlamp) biomicroscopic findings in all patients with corneal dystrophies. In addition, confocal microscopy provided more detailed images particularly of epithelial and stromal changes. CONCLUSION: Our data indicate that confocal microscopy provides information on living tissue that correlates with that obtained with conventional techniques on fixed and sectioned tissue.

Nuclear inheritance of a gene affecting mitochondrial gene expression.

Due to a deficiency in mitochondrial protein synthesis, Chinese hamster lung (CHL) cell mutant Gal- 32 does not grow in galactose or fructose. This report examines the nuclear or cytoplasmic inheritance of this single, recessive mutation. In a control experiment, fusion of Gal+TGSTK- cells with Gal- 32TGRTK+ cells resulted in tetraploid hybrids (as verified by karyotyping) that were selected in hypoxanthine/aminopterin/thymidine medium. The majority (2/3) of the control hybrids grew in galactose as expected since Gal+ is dominant over Gal-. Fusion of Rhodamine 6-G treated Gal+TGSTK- cells with Gal- 32TGRTK+ cells resulted in Rhodamine 6-G-tetraploid hybrids that were selected in hypoxanthine/aminopterin/thymidine medium. The majority (7/12) of the Rhodamine 6-G-hybrids grew in galactose as expected for a nuclearly encoded gene considering that Rhodamine 6-G interferes with transmission of mtDNA but not nuclear DNA. Therefore, these results are compelling in their demonstration of the nuclear origin of the Gal- 32 mutation.