Regioselective Partial Hydrogenation and Deuteration of Tetracyclic (Hetero)aromatic Systems Using a Simple Heterogeneous Catalyst.

The introduction of added '3-dimensionality' through late-stage functionalisation of extended (hetero)aromatic systems is a powerful synthetic approach. The abundance of starting materials and cross-coupling methodologies to access the precursors allows for highly diverse products. Subsequent selective partial reduction can alter the core structure in a manner of interest to medicinal chemists. Herein, we describe the precise, partial reduction of multicyclic heteroaromatic systems using a simple heterogeneous catalyst. The approach can be extended to introduce deuterium (again at late-stage). Excellent yields can be obtained using simple reaction conditions.

Defining the role of echinocandin catechol functional groups in the development of secondary hepatocellular carcinoma.

OBJECTIVES: To determine whether the catechol functional group on echinocandins decreases the catechol-O-methyltransferase (COMT) metabolism of catechol oestrogens (CEs) and the potential role of this functional group in the development of hepatocellular cancer. METHODS: Human COMT expression was measured by RT-PCR in a panel of selected human cancer cell lines and human hepatocytes. An ex vivo human hepatocyte model was employed to evaluate the metabolism of 17-ß-oestradiol to CEs in the presence of a catechol (B(0)C) versus a non-catechol echinocandin (B(0)) compound. COMT inhibition assays were conducted to evaluate the metabolism of CEs in the presence of B(0)C or B(0). Oestrogen receptor expression in human hepatic carcinoma cells was evaluated by RT-PCR and western blotting. Cell proliferation assays were used to evaluate the impact of B(0) or B(0)C on cancer cell growth. RESULTS: MCF-7 and Hep-G2 cells and human hepatocytes expressed variant Met/Met COMT. At clinically relevant concentrations, only B(0)C significantly increased CE levels in the COMT inhibition assays, to 90.0 µM compared with 79.8 µM in the untreated controls (P = 0.032). A high concentration (500 µg/mL) of B(0)C decreased COMT expression to 79%, 94% and 90% of untreated, baseline control levels in the three cell lines, respectively. B(0)C and B(0) did not increase cell growth in the cancer cell lines evaluated. CONCLUSIONS: At clinically achievable concentrations only B(0)C significantly inhibited COMT activity and increased CE concentrations. Short-term exposure did not alter the rate of cancer cell growth. Confirmation is needed to determine the clinical impact of long-term exposure to and the use of echinocandins with catechol functional groups.

Recommended community strategies and measurements to prevent obesity in the United States.

Approximately two thirds of U.S. adults and one fifth of U.S. children are obese or overweight. During 1980--2004, obesity prevalence among U.S. adults doubled, and recent data indicate an estimated 33% of U.S. adults are overweight (body mass index [BMI] 25.0-29.9), 34% are obese (BMI >or=30.0), including nearly 6% who are extremely obese (BMI >or=40.0). The prevalence of being overweight among children and adolescents increased substantially during 1999-2004, and approximately 17% of U.S. children and adolescents are overweight (defined as at or above the 95% percentile of the sex-specific BMI for age growth charts). Being either obese or overweight increases the risk for many chronic diseases (e.g., heart disease, type 2 diabetes, certain cancers, and stroke). Reversing the U.S. obesity epidemic requires a comprehensive and coordinated approach that uses policy and environmental change to transform communities into places that support and promote healthy lifestyle choices for all U.S. residents. Environmental factors (including lack of access to full-service grocery stores, increasing costs of healthy foods and the lower cost of unhealthy foods, and lack of access to safe places to play and exercise) all contribute to the increase in obesity rates by inhibiting or preventing healthy eating and active living behaviors. Recommended strategies and appropriate measurements are needed to assess the effectiveness of community initiatives to create environments that promote good nutrition and physical activity. To help communities in this effort, CDC initiated the Common Community Measures for Obesity Prevention Project (the Measures Project). The objective of the Measures Project was to identify and recommend a set of strategies and associated measurements that communities and local governments can use to plan and monitor environmental and policy-level changes for obesity prevention. This report describes the expert panel process that was used to identify 24 recommended strategies for obesity prevention and a suggested measurement for each strategy that communities can use to assess performance and track progress over time. The 24 strategies are divided into six categories: 1) strategies to promote the availability of affordable healthy food and beverages), 2) strategies to support healthy food and beverage choices, 3) a strategy to encourage breastfeeding, 4) strategies to encourage physical activity or limit sedentary activity among children and youth, 5) strategies to create safe communities that support physical activity, and 6) a strategy to encourage communities to organize for change.