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New More Effective Antimicrobials Might Rise From Old

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By tinkering with their chemical structures, researchers at the University of California, San Diego School of Medicine have essentially re-invented a class of popular antimicrobial drugs, restoring and in some cases, expanding or improving, their effectiveness against drug-resistant pathogens in animal models.

Writing in the October 7 Early Edition of PNAS, Lars Eckmann, MD, professor of medicine, and colleagues describe creating more than 650 new compounds by slightly altering structural elements of metronidazole and other 5-nitromidazoles (5-NI), a half-century-old class of antimicrobial drugs used to combat everything from an ulcer-causing stomach bacterium to a gut-churning protozoan found in contaminated water.

“The basic building blocks of 5-NI drugs are the same for all. We decorated around them, adding extra molecular pieces to change their shapes and sizes,” said Eckmann, who published the paper with colleagues at UC San Diego, The Scripps Research Institute and the Queensland Institute of Medical Research in Australia. The result: The altered shapes changed how many of the new compounds attacked pathogens in animal models, overcoming previous microbial resistance.

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