11-Aminostrychnine and N-(Strychnine-11-yl)propionamide: Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors.

(11S)-11-Aminostrychnine (1) and N-[(11S)-strychnine-11-yl]propionamide (2) were synthesized and characterized as antagonists of homomeric α1 and heteromeric α1ß glycine receptors in a functional fluorescence-based assay and a patch-clamp assay and in radioligand binding studies. The absolute configuration at C-11 of 1 was determined based on vicinal coupling constants and NOESY data. Docking experiments to the orthosteric binding site of the α3 glycine receptor showed a binding mode of compound 2 analogous to that of strychnine, explaining its high antagonistic potency. The findings identify the C-11 amide function of strychnine as a suitable linker group for the future development of dimeric strychnine analogues targeting glycine receptors. The findings extend the SAR of strychnine at glycine receptors.

Cytotoxicity and anti-inflammatory activity of methylsulfanyl-triazoloquinazolines.

A series of twenty five 2-methylsulfanyl-[1,2,4]triazolo[1,5-a]quinazoline derivatives 1-25 was previously synthesized. We have now investigated their cytotoxic effects against hepatocellular Hep-G2 and colon HCT-116 carcinoma cells and effect on the macrophage growth, in addition to their influence of the inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α (TNF-α), prostaglandin E-2 (PGE-2) and in bacterial lipopolysachharide (LPS)-stimulated macrophages]. The findings revealed that compounds 13 and 17 showed the highest cytotoxicity and that 3, 6-8 and 25 are promising multi-potent anti-inflammatory agents.

Methylcellulose, a healing inhibitor factor in an animal model of trabeculectomy.

PURPOSE: To use an experimental animal model to study the effect on intraocular pressure (IOP) of methylcellulose 2% application in trabeculectomy, followed by histologic assessment. METHODS: Trabeculectomy was performed on albino rabbits' eyes. The study comprised two groups, each group consisting of five rabbits. The right eyes were subjected to trabeculectomy, and the left eyes served as the control. In both groups 1 and 2, trabeculectomy was performed in the right eyes, but in group 2, trabeculectomy was followed by injection of methylcellulose 2% into the anterior chamber. The methylcellulose was allowed to pass through the trabeculectomy site into the subconjunctival space, and an extra amount was injected by the same cannula under the conjunctiva in the area of the trabeculectomy from the edge of the periotomy. Measurement of IOP was performed with a Shiotz tonometer once weekly for 4 weeks. Specimens were obtained from the operative site, and semithin sections were prepared, stained with toluidine blue, and examined by light microscopy (LM). RESULTS: A significant difference in the decrease of IOP (P<0.0001) was observed between the two groups after 4 weeks of surgery. During the 4 weeks after trabeculectomy, the mean IOP was 18.2+/-0.45 mm Hg without methylcellulose injection and 18.3+/-0.77 mm Hg in the control eyes, and 9.8+/-0.84 mm Hg with methylcellulose injection, 18.25+/-0.7 mm Hg in the control eyes. The histopathological findings in group 1 (without methylcellulose injection) showed the subscleral spaces to be less fenestrated, with deposition of dense collagen bundles intermingled with the fibrocytes, some of which were active with prominent mitosis. In contrast, in group 2 (injected with methylcellulose), the subscleral space appeared fenestrated with irregularly and widely spaced segmented collagen bundles. CONCLUSIONS: Methylcellulose may have antihealing properties that serve to decrease IOP in trabeculectomy. Although more work is needed in humans, because human tissue may be different in its response to the same procedure, the use of methylcellulose could be very promising.

Effect of P2O5 and MnO2 on crystallization of magnetic glass ceramics.

This work pointed out the effect of adding P2O5 and/or MnO2 on the crystallization behavior of magnetic glass ceramic in the system Fe2O3·ZnO·CaO·SiO2·B2O3. The differential thermal analysis of the quenched samples revealed decrease in the thermal effects by adding P2O5 and/or MnO2 to the base sample. The X-ray diffraction patterns show the development of nanometric magnetite crystals in a glassy matrix. Heat treatment at 800 °C for 2 h, under reducing atmosphere, caused an increase in the amount of the crystallized magnetite with the appearance of minor hematite and Ca2SiO4. The transmission electron microscope revealed a crystallite size in the range 10-30 nm. Magnetic hysteresis cycles were analyzed with a maximum applied field of 25 kOe at room temperature. The prepared magnetic glass ceramics are expected to be useful for localized treatment of cancer.