Novel indoline derivatives prevent inflammation and ulceration in dinitro-benzene sulfonic acid-induced colitis in rats.

Background: In search of safer treatments for inflammatory bowel disease in subjects not responding to, or showing adverse effects to TNF-α antagonists, we tested three novel indoline carbamates in the 2,4-dinitrobenzene sulfonic acid (DNBS) model of colitis in rats. The compounds have anti-inflammatory activity in other disease models in mice.

Methods: AN827 (3-(2-(methoxy carbonyl) ethyl) indolin-4-ylethyl methyl) carbamate (0.

The anti-inflammatory activity of a novel fused-cyclopentenone phosphonate and its potential in the local treatment of experimental colitis.

A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity and in vivo (DNBS induced rat model) for its potential to ameliorate induced colitis. Specifically, the competence of P-5 to reduce TNFα, IL-6, INFγ, MCP-1, IL-1α, MIP-1α, and RANTES in LPS-activated macrophages was measured. Experimental colitis was quantified in the rat model, macroscopically and by measuring the activity of tissue MPO and iNOS and levels of TNFα and IL-1β.

Dose-limiting inhibition of acetylcholinesterase by ladostigil results from the rapid formation and fast hydrolysis of the drug-enzyme complex formed by its major metabolite, R-MCPAI.

Ladostigil is a pseudo reversible inhibitor of acetylcholinesterase (AChE) that differs from other carbamates in that the maximal enzyme inhibition obtainable does not exceed 50-55%. This could explain the low incidence of cholinergic adverse effects induced by ladostigil in rats and human subjects. The major metabolite, R-MCPAI is believed to be responsible for AChE inhibition by ladostigil in vivo.

Multi-modal detection of colon malignancy by NIR-tagged recognition polymers and ultrasound contrast agents.

To increase colonoscopy capability to discriminate benign from malignant polyps, we suggest combining two imaging approaches based on targeted polymeric platforms. Water-soluble cationized polyacrylamide (CPAA) was tagged with the near infrared (NIR) dye IR-783-S-Ph-COOH to form Flu-CPAA. The recognition peptide VRPMPLQ (reported to bind specifically to CRC tissues) was then conjugated with the Flu-CPAA to form Flu-CPAA-Pep which was then incorporated into echogenic microbubbles (MBs) made of polylactic acid (PLA) that are highly responsive to ultrasound.

Synthesis and in vitro evaluation of anti-inflammatory activity of ester and amine derivatives of indoline in RAW 264.7 and peritoneal macrophages.

Unlabelled: A prolonged increase in pro-inflammatory cytokines, TNF-α and IL-6 occurs in inflammatory diseases. Although existing therapies like steroids and TNF-α antagonists are effective they may cause serious adverse effects. We describe the preparation and evaluation for anti-inflammatory activity of 11 novel derivatives of indoline carbamates with a propionic ester, 2-aminoethyl, 3-aminopropyl 2-(dimethylamino)ethyl or 3-(dimethylamino)propyl group in positions 3 or 1.

The relative roles of charge and a recognition peptide in luminal targeting of colorectal cancer by fluorescent polyacrylamide.

Real time detection of biomarkers at the mucosal level is imperative for the prevention and efficient treatment of colorectal cancer. Cationized polyacrylamide (CPAA) with increasing charge densities was prepared by radical polymerization of acrylamide and different mol% ratios of N-acryloyl, N'-(tert-butyl-carbonyl) diaminoethane. The NIR fluorophore derivative of IR-783, IR-783-S-Ph-COOH, was attached to the CPAA to give CPAA-783.

Mo(CO)6-mediated intramolecular Pauson-Khand reaction of substituted diethyl 3-allyloxy-1-propynylphosphonates.

Cyclisation of diethyl 3-allyloxy-1-propynylphosphonates with Mo(CO)(6) under PK conditions to give 3-substituted-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate, 2a-h, in 45-88% isolated yields was done. The R groups are always syn with H(b) (where applicable). The stereochemistry was determined via both NMR and crystal X-ray analysis.