InternetChemistry - Current Chemistry News of the Week

Potential new drugs: 970 million and still counting

Like astronomers counting stars in the familiar universe of outer space, chemists in Switzerland are reporting the latest results of a survey of chemical space - the so-called chemical universe where tomorrow's miracle drugs may reside. The scientists conclude, based on this phase of the ongoing count, that there are 970 million chemicals suitable for study as new drugs. Scheduled for the July 1 issue of the Journal of the American Chemical Society, the study represents the largest publicly available database of virtual molecules ever reported, the researchers say.

Jean-Louis Reymond and Lorenz Blum point out that the rules of chemical bonding allow simple elements such as carbon, hydrogen, oxygen, nitrogen and fluorine to potentially form millions of different molecules. This so-called "chemical universe" or "chemical space" has an enormous potential for drug discovery, particularly for identifying so-called "small molecules" - made of 10 to 50 atoms. Most of today's medicines consist of these small molecules. Until now, however, scientists had not attempted a comprehensive analysis of the molecules that populate chemical space.

In the report, Reymond and Blum describe development of a new searchable database, GDB-13, that scientists can use in the quest for new drugs. It consists of all molecules containing up to 13 atoms of carbon, nitrogen, oxygen, sulfur, and chlorine under rules that define chemical stability and synthetic feasibility. The researchers identified more than 970 million possible structures, the vast majority of which have never been produced in the lab. Some of these molecules could lead to the design and production of new drugs for fighting disease, they say.

Journal of the American Chemical Society: "970 Million Druglike Small Molecules for Virtual Screening in the Chemical Universe Database GDB-13" [J. Am. Chem. Soc., 2009, 131 (25), pp 8732–8733; DOI: 10.1021/ja902302h].

Successful initial safety tests for genetically-modified rice that fights allergy

In a first-of-its-kind advance toward the next generation of genetically modified foods - intended to improve consumers' health - researchers in Japan are reporting that a new transgenic rice designed to fight a common pollen allergy appears safe in animal studies. Their report is in the current issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.

Fumio Takaiwa and colleagues note that the first generation of genetically-modified crops was designed to help keep crops weed and insect free. The next generation of transgenic crops is being developed to directly benefit human health. This includes veggies and grains that produce higher levels of nutrients, such as vitamins and minerals, or even medicines and vaccines. Like the first generation of transgenic foods, however, researchers are anxiously trying to determine whether foods produced from these "biopharmaceutical" crops will be safe for humans and the environment.

The scientists describe development of a transgenic rice plant that has been genetically- engineered to fight allergies to Japanese cedar pollen, a growing public health problem in Japan that affects about 20 percent of the population. In laboratory studies, the researchers fed a steamed version of the transgenic rice and a non-transgenic version to a group of monkeys everyday for 26 weeks. At the end of the study period, the test animals did not show any health problems, in an initial demonstration that the allergy-fighting rice may be safe for consumption, the researchers say.

Journal of Agricultural and Food Chemistry: "26-Week Oral Safety Study in macaques for Transgenic Rice Containing major Human T-Cell Epitope Peptides from Japanese Cedar Pollen Allergens" [J. Agric. Food Chem., 2009, 57 (12), pp 5633–5638; DOI: 10.1021/jf900371u].

Brittle table salt can stretch like taffy in the nanoworld

Researchers in New Mexico are reporting the surprise discovery that common table salt - so brittle that it crushes easily between a thumb and forefinger - becomes a super plastic in the weird environs of the nanoworld. The super-elastic salt can stretch like taffy to twice its original length without breaking. The discovery could lead to new insights into the role of salt in a wide variety of situations ranging from helping clouds to form to triggering asthmatic attacks in people, they say. Their study is in the current issue of ACS' Nano Letters, a monthly journal.

Nathan Moore and colleagues note in the new study that researchers have known for years that metals like gold, lead and aluminum can be pulled into nanowires 1/50,000th the width of a human hair. Like other materials of such tiny dimensions, their properties change. Materials that conduct electricity poorly, for instance, become good conductors and materials that break easily develop new strength. That's why nanomaterials may form the basis of futuristic technologies that spawn new industries. But until now, no one expected to create nanowires from crystals of common table salt, or sodium chloride, which crumbles so easily.

The scientists made the unusual discovery while studying how water coats salt crystals using a microscope specially designed to observe mechanical and adhesive forces. They detected an unusual attractive force between the diamond tip of the microscope and the salt surface. After a series of tests, the researchers showed that the force encountered may have been caused by the presence of salt nanowires. In a similar test, they were able to capture images of salt nanowires being formed and stretched. The finding is "a striking and unexpected example of how material properties can change when viewed at the nanoscale," the article states.

Nano Letters: "Superplastic Nanowires Pulled from the Surface of Common Salt" [Nano Lett., 2009, 9 (6), pp 2295–2299; DOI: 10.1021/nl9004805].

Once-a-month pill for both fleas and ticks in Fido and Fluffy

Scientists in New Jersey are describing discovery and successful tests of the first once-a-month pill for controlling both fleas and ticks in domestic dogs and cats. Their study is in the current issue of ACS' Journal of the Medicinal Chemistry, a bi-weekly publication.

Peter Meinke and colleagues at Merck Research Laboratories note the need for better ways of controlling fleas and ticks, driven in part by increases in pet ownership. Estimates suggest that there were 71 million pet dogs and 81 million pet cats in the United States alone in 2007 - up from 61 million and 70 million in 2001. Although many powders, sprays and other topical agents are on the market, many pet owners prefer the convenience of pills. Products given orally can reach more parts of an animal's body, do not wash off in rain or bath water, and don't transfer from pets to people. At least one existing pill fights fleas in pets, but does not appear effective for ticks.

In tests on fleas and ticks in dogs and cats, a single dose of the new pill was 100 percent effective in protecting against both fleas and ticks for a month. There were no signs of toxic effects on the animals. Scientists obtained the flea and tick fighter from a substance first found in a fungus that "has the potential to usher in a new era in the treatment of ecoparasitic [ticks and fleas, for instance] infestations in companion animals."

Journal of Medicinal Chemistry: "Discovery of the Development Candidate N-tert-Butyl Nodulisporamide: A Safe and Efficacious Once Monthly Oral Agent for the Control of Fleas and Ticks on Companion Animals" [J. Med. Chem., 2009, 52 (11), pp 3505–3515; DOI: 10.1021/jm801334v].

Other "-caines" often replace Novocaine in the dentist's office

Novocaine? Not necessarily. The widespread belief that dentists rely on Novocaine to make those office visits almost painless needs some updating, according to an article scheduled for the June 29 issue of Chemical & Engineering News, ACS' weekly newsmagazine. In fact, patients are more likely to get any of several other anesthetics than the century-old standby Novocaine, which once reigned as the archetypal dental anesthetic.

C&EN senior editor Elizabeth Wilson notes that Novocaine, also known as procaine, has become a catchall term for a variety of dental anesthetics widely used today. These substances include less-familiar names like benzocaine, lidocaine, articaine, and mepivacaine. Like Novocaine, all are non-addictive relatives of the original, naturally occurring local anesthetic cocaine, which is found in coca leaves.

None of the newer local anesthetics are perfect, leading scientists to seek better medications that are faster-acting, more effective, and safer. Wilson's article describes not only this ongoing quest, but also research to determine exactly how dental anesthetics work in the body.

Chemical & Engineering News: "Dental anesthetics".