Wheaton Professor Discovers a New Class of Drug Leads Against Tuberculosis

A professor from the Chemistry department of Wheaton College, IL, along with his collaborators from the Institute for Tuberculosis Research, Chicago, have discovered a class of new compounds which have been shown to effectively kill the bacteria that causes tuberculosis (TB).

The discovery is significant because the new compounds made were also effective at killing strains of the bacteria that are resistant to popular TB drugs such as Isoniazid and Rifampin. TB is in fact curable and there are good TB drugs in use, however, tuberculosis has remained a serious global health issue because of complications resulting from the emergence of multi-drug resistant or even extremely multi-drug-resistant strains of Mycobacterium tuberculosis, the bacteria that causes TB. This means that if a person is infected with the kind of bacteria that is resistant to known drugs, that person will not respond to treatment with existing drugs, resulting in higher death rates. In such cases, doctors would often combine two or more different tuberculosis drugs to kill the bacteria.

Results of the latest discovery was published in the European Journal of Medicinal Chemistry, titled, Discovery of ultra short β-peptoids with selective activity against drug-resistant Mycobacterium tuberculosis.

According to Dr. Francis E. Umesiri, the lead author and principal investigator of the study, "The potential impact of this study is three-fold. First, the compounds designed and made in our lab are a new class of ultra short beta-peptoids. Second, these beta-petoids are relatively easy and cheaper to make and would pose no difficulty developing them into drugs should the need arise. Third, and most important, these new compounds showed potent activity against strains mono-resistant to isoniazid and rifampin, and against five of the global clades of Mycobacterium tuberculosis." Continuing, Dr. Umesiri noted that "Since this bacterium can develop resistance even to new drugs, it highlights not only the precarious nature of the battle against multi-drug resistance but also the need to develop truly first-in-class TB drugs with new and unique mechanism of action that evades bacterial resistance. Therein lies the potential significance of the current study."

The implications of studies like these are a matter of life and death for millions of people all over the world battling with TB. According to the latest World Health Organization TB Facts as at the time of publication:

Tuberculosis is the leading cause of death from a single infectious disease worldwide.
10 million people worldwide were sick with TB in 2023.
1.25 million people died from tuberculosis in 2023 alone.
Close to one-third (1/3) of the world's population is infected with the latent form of the bacteria.

Most of the deaths resulting from TB are from developing countries in Asia, Africa, and South America.
In fact, according to WHO global TB report, 56% of those who developed the disease in 2023 lived in just 5 countries: India (26%), Indonesia (10%), China (6.8%), the Philippines (6.8%), and Pakistan (6.3%).

Drug-resistance to current medications is a major complication in eradicating this disease once and for all.

Therefore, considering such adverse and global impact of TB, any effort towards discovery of new drugs that are effective against drug-resistant strains of the bacteria is a big deal. Although the new class of compounds discovered by Dr. Umesiri and his collaborators are far from making their way into a final TB drug regimen, they provide scientists a set of lead compounds with which to keep tinkering until more effective drug compounds are developed. This is what scientists call lead optimization in the drug discovery process.

Finally, the discovery of these new TB drug leads demonstrates the power of collaboration in science. In this case, the collaboration is between an organic synthetic lab, led by Dr. Umesiri, where the compounds were designed and made, and the microbiology lab at the Institute for Tuberculosis Research, led by Dr. Scott Franzblau, where extensive biological screenings were undertaken.

Learn more at: https://authors.elsevier.com/a/1kqPf_55HFRqF8

For further enquiries, contact: Dr. Francis E. Umesiri, Chemistry department, Wheaton College, IL.

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This release was published on openPR.