Cryptosporidiosis is a leading waterborne infection caused by the Cryptosporidium parasite that results in diarrhea, dehydration, and malnutrition. In severe cases, the parasitic infection can lead to death, most notably in young children and immunocompromised patients. Nitazoxanide is an FDA-approved treatment, but is only modestly effective, suggesting a critical need for a new anti-Cryptosporidium drug that effectively treats all patient populations. Previous work identified triazolopyridazine MMV665917 as a hit compound for anti-Cryptosporidium drug discovery, which has an EC50 of 2.1 μM. This finding led to the synthesis of SLU-10482, an analogue with an improved EC50 of 0.070 μM. The current work seeks to replace the 3-trifluoromethyl group on SLU-10482 and develop structure-activity relationships (SAR) in that position. Twenty-six novel analogues were synthesized and evaluated for potency against Cryptosporidium, with the most potent replacement to date being the propylene SLU-11358 analogue (EC50 = 0.56 μM).

Dr. Meyers was influential in assisting Caitlin with her presentation and her research over the past three years. She is grateful for his guidance and support that was constant throughout her research.