Issue Date: December 19, 2011
Hitting Tuberculosis With A Toxic Gas
Pointing to a new avenue of tuberculosis drug research, a team of researchers in India reports that small amounts of sulfur dioxide can slow the growth of the bacterium that causes the disease (J. Med. Chem., DOI: 10.1021/jm201023g). Led by Harinath Chakrapani of the Indian Institute of Science Education & Research, the researchers were inspired by a TB drug in clinical trials that works by releasing small amounts of toxic nitric oxide. Chakrapani wanted to try the same approach with SO2, which among other applications finds use as an antibiotic in wine making. The team investigated 2,4-dinitrophenylsulfonamides, which can react with thiols to release SO2. The researchers added solutions of 11 SO2-producing molecules to Mycobacterium tuberculosis colonies. After 28 days, they saw that the molecules that released the most SO2 also were the best at inhibiting the growth of the bacteria. The most potent molecule (shown) slowed growth at lower concentrations than the standard TB drug isoniazid did: At 0.37 µM, isoniazid reduced growth by 99%, whereas the best sulfonamide reached the same level of inhibition at 0.15 µM. The active molecules are as much as 50 times more toxic to M. tuberculosis than to human cells, Chakrapani and coworkers found.
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