Back in the game

Thanks to a bit of chemical tinkering, weapons that had lost a lot of its power to the growing phenomenon of drug resistance may be able to return to the front line of the war against pathogens such as bacteria and parasites.Someone, however, will need to be willing to spend a lot of money to get these newly created drug compounds developed and approved for clinical use.Researchers at the University of California, San Diego School of Medicine, in conjunction with collaborators at the Scripps Research Institute and the Queensland Institute of Medical Research, in Australia, reported Oct. 7 in the journal Early Edition of PNAS they have created some 650 potentially useful drug compounds by chemically altering metronidazole and other members of the 5-nitromidazole class of antibiotics.

Developed some 50 years ago, these 5-NI antibiotics have been used to treat various bacteria and parasites. Some 5-NI targets have included Helicobacter pylori, a bacterium that causes stomach ulcers and cancer, and Giardia lamblia, a water-borne parasite that causes diarrheal diseases.Now, however, some diseases are growing resistant to 5-NI drugs. For example, in developing countries, nearly half of H. pylori infections are 5-NI resistant. In addition, resistance is a problem in one-out-of-five cases of Trichomonas vaginalis, a sexually transmitted parasite that causes ailments of the urogenital tract, and Giardia lamblia.

“Antibiotic resistance is rising for many different pathogens that are threats to health,” said Tom Frieden, director of the federal Centers for Disease Control and Prevention. “If we don’t act now, our medicine cabinet will be empty and we won’t have the antibiotics we need to save lives.”As part of their anti-resistance efforts, Lars Eckmann, a UCSD School of Medicine professor, and his colleagues began experimenting with changes to the chemical structure of 5-NI drugs to see how they performed against resistant patogens in animals models.

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