Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma.

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, develo…

ASYMMETRIC SYNTHESIS OF LINEZOLID THROUGH CATALYZED HENRY REACTION

Linezolid 1 is an antibacterial oxazolidinone approved by FDA in 2000 for the treatment of fastidious bacterial infections.1 The asymmetric synthesis of Linezolid-like molecules make use of the chiral pool approach, through the so-called Manninen reaction.2 This strategy requires the use of BuLi, low temperature and a long elaboration of the acetamide chain. Curiously, the only catalyzed approach toward the asymmetrical synthesis of Linezolid was just recently reported, and belongs to the use of proline-derived catalysts in aldol reactions as the key step.3 This procedure is quite interesting except for the low yield. Here we report a new synthesis of Linezolid, based on a Cu(II)-catalyzed …

SYNTHESIS AND EVALUATION OF CURCUMIN ANALOGUES AS NEURO-PROTECTIVE AGENTS FOR THE ALZHEIMER'S DISEASE

The Alzheimer's disease (AD) is the most common form of senile dementia.1 The most important role in AD is played by the aggregation process of beta-amyloid peptide (Aß), responsible for the cytotoxic effects.2 In this context, the purpose of this study was to synthesize new dicarbonyl compounds 1 structurally related to curcumin3, with anti-aggregation activity against Aß.Parallel studies involve the synthesis of heterocyclic-based curcumin-like molecules that are currently under investigation by means of in silico protocols in order to rationalize the ligand-biological target interactions.

Asymmetric synthesis and biological evaluation of 1,2,4-Oxadiazoles analogues of Linezolid

Oxazolidinones are a class of antibacterial agents which displayed activity againist a variety of gram-positive pathogens and are highly potent against multidrug-resistant bacteria. Linezolid is the first oxazolidinone antibiotic approved for clinical use but linezolid resistance began to appear. 1,2,4 – Oxadiazoles are known bioactive heterocycles whose activity has been often associated to their bioisosterism with amide or ester functionalities [1]. As results of a research project on the molecular design of heterocycle – based antibacterials to contrast Multi-Drug Resistance (MDR) [2], we report the synthesis of 1,2,4 - Oxadiazole analogues of Linezolid. The synthesis has been achieved b…

Cytokine Gene Polymorphisms and Breast Cancer Susceptibility

Human breast cancer (BC) is characterized by a considerable clinical heterogeneity. Steroid hormone receptor expression and growth factor receptor expression have been considered suitable diagnostic and prognostic markers, whereas mutations of oncosuppressor and gatekeeper genes have been found associated with an increased risk for this malignancy. To evaluate the role that polymorphisms of genes involved in the regulation of inflammatory response might play in BC susceptibility, we investigated associations between cytokine functionally relevant polymorphisms in 84 BC patients compared to 110 age- and sex-matched controls. TNF-alpha (-308G/A), TGF-beta1 (+869C/T), IL-10 (-1117G/A; -854C/T;…

Sintesi di analoghi eterociclici del Linezolid di interesse biologico

Applications of ring rearrangements involving a participating side chain for the synthesis of five-membered heterocycles

Concise asymmetric synthesis of Linezolid through catalyzed Henry reaction

A new asymmetric synthesis of the antibiotic Linezolid was performed through a copper-catalyzed Henry reaction as the key step. The use of camphor-derived aminopyridine ligands helped to improve the yields of the chiral precursor and to obtain Linezolid in good overall yield and enantiomeric excess.