Chemistry major Catherine Pugh ’19 has spent the past year studying the modification of sulfonamides (sulfa drugs), a kind of antibiotic that was among the first widely used antibacterial drugs in the US, to combat drug-resistant tuberculosis (TB).
“[Sulfa drugs] were used to treat everything, but they fell out of fashion as we developed targeted drugs to fight specific diseases,” she explained. “But there’s been some recent literature suggesting that they can be modified to be active against tuberculosis, which can be a really difficult disease to treat.”
A 2016 paper published by scientist Joshua Thiede in “Nature” was among the most recent to suggest that sulfa drugs may be able to serve as a base for antibiotics that treat tuberculosis. A new kind of antibiotic targeting TB is badly needed, as over the years more and more drug-resistant strains have emerged. Drug resistance spreads when bacteria mutate to reduce the effectiveness of a given antibiotic; their resistance allows them to survive and multiply. This often leads to an arms race between scientists developing new antibiotics and bacteria developing new mutations. Often, the longer an antibiotic is popular, the less effective it becomes.
“[TB] is resistant to a lot of normal antibacterial drugs, and the drugs that we’re using to treat TB right now are the same drugs that we’ve been using since the 1950s, so it’s definitely an area that needs to be refreshed,” said Pugh. “There have been new drugs that have been created, there have been some attempts to find a vaccine, but it’s been really difficult to treat.”
One of the reasons for this difficulty, explained Pugh, is that TB is a mycobacterium, meaning that its cell wall is unusually thick and therefore difficult to penetrate with antibiotics. It can also remain in stasis in an infected person’s body for long periods of time before symptoms begin to show, making it harder to contain.
Pugh is interested in this particular disease in part because TB has been under-researched, due to the fact that it rarely affects those in wealthy countries.
“Tuberculosis is not seen as a problem in white, middle-class America anymore, because it’s largely been eradicated through prevention,” she explained. “These days it’s affecting countries that are industrializing now — poorer countries, and people in the U.S. of lower socioeconomic status or who are immunocompromised. So it’s still a problem, but not as much money is being allocated to treat it.”
One of the chemists who has been working on this problem is Professor Michael Hearn, who agreed to be Pugh’s thesis advisor despite recently retiring.
“He’s been working in anti-tuberculosis drugs for a really long time,” she said. “When I joined [his lab], I think he was just beginning exploration into sulfa drugs specifically. He’s previously done work on modification of other anti-tubercular drugs, and he’s published results on those.”
Hearn was a fitting advisor because his class made Pugh realize her interest in organic chemistry in the first place.
“I had had Professor Hearn for my Organic [Chemistry] I class, and I was interested in organic chemistry research because I discovered much to my surprise that I was interested in organic chemistry,” she said. “I took chem in 10th grade, and then in 11th grade I took AP chem and decided that I hated organic chemistry and was interested in inorganic chemistry.”
In Hearn’s class, however, Pugh realized that what she had hated about organic chemistry in high school was that introductory-level organic chemistry req uires large amounts of memorization. At higher levels, she said, chemistry is much more logic-based and requires more creativity.
For her thesis, Pugh’s research method involved modifying seven different sulfa drugs and then testing their effectiveness compared to the unmodified drugs to see if the modifications had made the drugs more effective. Because tuberculosis is a “pretty nasty disease,” as Pugh puts it, she and Hearn were mainly responsible for the modifications rather than the biological testing, which was done by Dr. Michael Synamon in Syracuse, NY.
“We ship off our samples to him once we have isolated, purified and characterized them,” Pugh explained.
Her thesis found that modifying certain molecular structures did indeed make sulfa drugs more effective against tuberculosis in a lab setting, which she is optimistic about because it could lead to a better understanding of what works against tuberculosis.
“There’s a couple drugs that we found that were significantly more effective. They also point towards what other modifications can further increase efficacy,” she said. “Drug design is sort of a stepped process; you make a whole bunch of different modifications of the drug at the same point, and then determine which is the most active against the disease…We’ve done a lot of the starting work there, in figuring out which solvents to use, which conditions [and] what reactants.”
After graduation, Pugh wants to work for a pharmaceutical company in drug design or drug exploration. She wants to “take a break from academia” for a few years to work in research.
She added that she loves Professor Hearn and feels that her experience at Wellesley has been a positive one due in large part to its size.
“I’m really appreciative of Wellesley as a small institution that only has undergraduates,” she said. “I am doing the research hands-on, I’m responsible for some of it, and I’m always talking to my professor about what it means.”