To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this "Connectivity Map" resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project.

http://cinjweb.umdnj.edu/sites/molmdweb/documents/connectivitymap.pdf

The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease

13C NMR spectra of pentacyclic triterpenoids--a compilation and some salient features

Biological activities and distribution of plant saponins.

Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

A review on the dietary flavonoid kaempferol.

Epidemiological evidence suggests that flavonoids may play an important role in the decreased risk of chronic diseases associated with a diet rich in plant-derived foods. Flavonoids are also common constituents of plants used in traditional medicine to treat a wide range of diseases. The purpose of this article is to summarize the distribution and biological activities of one of the most common flavonoids: luteolin. This flavonoid and its glycosides are widely distributed in the plant kingdom; they are present in many plant families and have been identified in Bryophyta, Pteridophyta, Pinophyta and Magnoliophyta. Dietary sources of luteolin include, for instance, carrots, peppers, celery, olive oil, peppermint, thyme, rosemary and oregano. Preclinical studies have shown that this flavone possesses a variety of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial and anticancer activities. The ability of luteolin to inhibit angiogenesis, to induce apoptosis, to prevent carcinogenesis in animal models, to reduce tumor growth in vivo and to sensitize tumor cells to the cytotoxic effects of some anticancer drugs suggests that this flavonoid has cancer chemopreventive and chemotherapeutic potential. Modulation of ROS levels, inhibition of topoisomerases I and II, reduction of NF-kappaB and AP-1 activity, stabilization of p53, and inhibition of PI3K, STAT3, IGF1R and HER2 are possible mechanisms involved in the biological activities of luteolin.

Distribution and biological activities of the flavonoid luteolin.

The isolation and structure elucidation of gedunin [1], the antimalarial agent of Azadirachta indica, are reported. Its 1H- and 13C-nmr spectra were assigned by using one- and two-dimensional nmr spectroscopy, especially homonuclear and heteronuclear COSY, nOe difference, and COLOC experiments.

Isolation and characterization of an antimalarial agent of the neem tree Azadirachta indica.

13 C NMR Chemical shifts and carbon-proton coupling constants of some furocoumarins and furochromones

The 13C chemical shifts of 209 naturally occurring and synthetic coumarin derivatives are listed and a number of methods for signal assignments are explained. Substituent effects on 13C chemical shifts (SCS) in monosubstituted coumarins and non-additivities of SCS in coumarins with more than one substituent are discussed in detail.

13C NMR spectroscopy of coumarin derivatives

Publisher Summary Selenium ( 77 Se) has attracted the widest nuclear magnetic resonance (NMR) spectroscopic interest among the group 16 elements. The most important 77 Se NMR parameter is the chemical shift reflecting the chemical environment around the selenium atom. Chemical shift tensors can be obtained from the rotational side-band pattern in solid-state 77 Se NMR spectra and offer more detailed information. Conformational analysis of selenium-containing compounds by temperature-variable NMR spectroscopy (DNMR) is facilitated by the great sensitivity of the 77 Se chemical shift. Generally, chemical shift differences of selenium atoms in different conformers (at low temperatures) are much larger than those of carbon or hydrogen atoms. Therefore, the coalescence temperature in 77 Se NMR spectra is higher than in 1 H or 13 C NMR experiments of the same compounds. The 77 Se NMR chemical shift tensors of a selection of inorganic and organic selenium-containing compounds have been obtained from solid-state NMR, partly involving cross-polarization (CP) and magic angle spinning (MAS). 77 Se NMR spectroscopy is recognized as a useful tool for the elucidation of molecular structures of selenium-containing compounds and intermediates. In other applications, 77 Se nuclei are used as probes for detecting molecular chirality, intramolecular interactions, or bond situations. In addition, some methods have been invented where selenium-containing auxiliaries are applied to selenium-free compounds.

Helmut Duddeck

Papers

Isolation and characterization of an antimalarial agent of the neem tree Azadirachta indica.

13 C NMR Chemical shifts and carbon-proton coupling constants of some furocoumarins and furochromones

13C NMR spectroscopy of coumarin derivatives

77Se NMR Spectroscopy and Its Applications in Chemistry

Structure elucidation by modern NMR