Hitting TB With Toxic Gas | Chemical & Engineering News
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Web Date: December 9, 2011

Hitting TB With Toxic Gas

Medicinal Chemistry: Small molecules that release sulfur dioxide could stop the growth of the bacteria that cause tuberculosis
Department: Science & Technology
News Channels: Biological SCENE
Keywords: tuberculosis, TB, sulfur dioxide, nitric oxide
Bacterial Scourge
The microbe that causes TB has increasingly become drug resistant, so new strategies are urgently needed against the disease.
Credit: CDC/Ray Butler, Janice Carr
20111209lnj1-Mycobacterium_tuberculosis
 
Bacterial Scourge
The microbe that causes TB has increasingly become drug resistant, so new strategies are urgently needed against the disease.
Credit: CDC/Ray Butler, Janice Carr
[+]Enlarge
Scourge To Bacteria
: Scourge To Bacteria Compared to a well-known anti-tuberculosis drug, researchers’ most potent molecule (6) required lower concentrations to stop bacteria in their tracks.
Credit: J. Med. Chem.
20111209lnj1-jm201023g-3
 
Scourge To Bacteria
: Scourge To Bacteria Compared to a well-known anti-tuberculosis drug, researchers’ most potent molecule (6) required lower concentrations to stop bacteria in their tracks.
Credit: J. Med. Chem.

Small amounts of sulfur dioxide can slow the growth of the bacteria that cause tuberculosis, researchers report (J. Med. Chem., DOI: 10.1021/jm201023g). The toxic gas could form a new avenue of drug research for the disease.

Researchers in India, led by Harinath Chakrapani at the Indian Institute of Science Education and Research Pune, were inspired by a drug in clinical trials for TB. It releases small amounts of nitric oxide, a toxic gas that can have beneficial physiological effects in small doses.

Chakrapani wanted to do the same with another toxic gas, SO2, which finds use as an antibiotic in winemaking. He investigated a family of 2,4-dinitrophenylsulfonamides that can react with thiols to release SO2. “Nobody has really thought of it before,” says Chakrapani.

To test the idea, the researchers added cysteine, a thiol-containing amino acid, to various 2,4-dinitrophenylsulfonamides to see which molecules produced the most SO2. The researchers then added solutions of 11 SO2-producing molecules to growing 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. What’s more, the most potent molecule slowed growth at lower concentrations than the standard tuberculosis drug isoniazid did: At 0.37 µM, isoniazid reduced growth by 99%, while the researchers’ compound reached the same level of inhibition at 0.15 µM. To rule out sulfite as the active agent, the researchers tested sulfite ions against the bacteria. Sulfite did not inhibit bacterial growth.

The active molecules are as much as 50 times more toxic to tuberculosis than to human cells, Chakrapani found. Chakrapani now wants to investigate related molecules, because the dinotrophenylsulfonamide structure, he says, “gives us a handle to tune the rate of SO2 generation using very simple structural changes.”

 
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Comments
Dr. HC Group IISER Pune. (December 13, 2011 4:47 AM)
Its really amazing to see our group work to be highlighted in C&EN. It is motivating us to get involved in many such exciting findings. Thanks for the encouragement.

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