Antibiotics have been taken on the chin lately. Not only drug resistance increases, but pharmaceutical companies have dropped antibiotic research programs because drugs are difficult and expensive to manufacture. Now, help is on the way. Researchers now report that they have found a way to multiply the new members of one of the most common classes of antibiotics called macrolides. The work could lead to new weapons against antibiotic-resistant infections, and maybe save millions of lives.
macrolides, medications that include erythromycin and azithromycin, were first developed in the 1950s Since then, they have become a bulwark against bacterial and fungal infections. Chemically, macrolides are giant rings containing 14 to 16 carbon atoms, with one or more sugar appendages that hang on the side. Bacteria synthesize them fight their neighbors. However, the bacteria did not evolve to make good macrolide drugs in people. So chemists medicinal group of researchers who are actually building new startup drug with natural versions and modify their links one at a time in an effort to make them safer and more efficient. But in most cases it is impossible to limit the changes to a single link on a large molecule. When multiple bonds are reacted, the result is an unwanted mixture wide finished product, none of which contain only a desired specific modification to make a better drug.
To solve this problem, a chemist at Harvard University Andrew Myers and his colleagues adapted a strategy of divide and rule they applied antibiotic tetracycline in 05. They started with three basic structures macrolide ring and broke down in each molecular eight modules "." They then carefully mapped reactions necessary to put the pieces together. For two of these linkers have even invented new chemical reactions to forge links so. This allowed them to tinker with the modules individually and then reassembled. Repeating the strategy several times, they forged more than 300 completely new macrolides.
When administered to a group of bacterial laboratory cultures, many of these compounds showed potent antibiotic activity against microbes resistant to antibiotics, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus reports online today in Nature of the team . Perhaps as important, Myers said, is that all reactions used to assemble produce high yields of the final products. This is essential, he notes, because bacteria do not produce the starting material for the novel compounds. So if one of them is a valuable medicinal chemists will be able to synthesize large quantities cheaply from scratch.
"This is an excellent example of the beautiful chemistry will have a tangible societal benefit," said Phil Baran, a chemist organic synthesis at the Scripps Research Institute in San Diego, California. Myers has set up a company, macrolides Pharmaceuticals, to market the work.
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