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Faculty Colloquium: Nawarathne meditates on medicinal chemistry

Drug-resistant bacteria are one of the most urgent public health issues in the world, and Assistant Professor of Chemistry Dr. Irosha Nawarathne and her students are researching solutions. 

Nawarathne opened the Faculty Colloquium lecture series on Sept. 13 with a discussion of her medicinal chemistry research, “Oh, The … You’ll See!” The blank in the title represented molecules, she said, because observing the interactions between drug molecules and the drug targets is key to medicinal chemistry.

In addition to the research on drug-resistant bacteria, Nawarathne’s research team works on developing new pharmaceuticals for lung cancer, the most frequent and deadly cancer type in Arkansas and the U.S. Nawarathne researched cancer as a graduate student at Michigan State University.

She explained that bacteria and viruses can develop a resistance to medications previously used for successful treatment, a process known as antimicrobial resistance.

“Having superbugs that can survive in the presence of antibiotics is a problem not only for public health but also for pharmaceutical companies,” Nawarathne said.

By the time antibiotics are put on the market, bacteria have often already gained resistance.

“If you spent 20 to 30 years making a chemical that can be an antibiotic, that’s a huge issue. You lost time and billions of dollars developing the antibiotic. This is a challenge we have to deal with as medicinal chemists.”

Nawarathne and her students focus on drug-resistant strains of tuberculosis (TB). Although many think the disease was wiped out, she said there were about 10 million cases and 1.3 million deaths from TB worldwide in 2017.

Multidrug-resistant TB (MDR TB) is resistant to at least two of the first-line drugs used for treatment, rifampin and izoniazid. Extensively drug-resistant TB (XDR TB) is resistant to most available treatment. 

Nawarathne said treating a single case of TB is expensive, costing about $19,000. A case of MDR TB costs about $164,000 to treat, she said, and a case of XDR TB costs about $526,000.

“You can imagine how much of a burden this can be for a country, especially developing countries, where they don’t have the money or treatments.”

Her research team has been working on the development of novel rifamycins, a group of antibiotics effective against Mycobacterium, to combat MDR TB strains by gaining a deeper understanding of molecular interactions between the rifamycins and the Mycobacterium RNA polymerase, an enzyme responsible for copying a DNA sequence into an RNA sequence.

The drugs stop the production of proteins by bonding to the RNA polymerase, killing the bacteria. If mycobacteria change the protein, chemists must change the drug accordingly in order for them to bind back together.

“If the drug is not effective, it won’t bind to the RNA. We go through several steps, from purification to analysis to activity tests to see if we have gotten the results we want.”

The research team patented a drug in 2018 that could be developed into an antibiotic to treat drug-resistant mycobacteria, she said. The team also has a research paper under review.

“We have made an array of molecules that could be developed to treat lung cancer, which have demonstrated promising anticancer activities against Lewis lung cancer line and also melanoma.”

Nawarathne said she has had the opportunity to work with more than 20 research students at Lyon and is thankful for their commitment to the project.

“I love watching them grow professionally and intellectually. I am so thankful for all of them and their enthusiasm, dedication, and encouragement.”

She is also grateful for the continuous support and funding from Arkansas IDea NetWork of Biomedical Excellence (INBRE), FutureFuel Chemical Company, Lyon College, and her collaborators at the University of Arkansas Medical Sciences, University of Michigan, and Michigan State University.