Cryptosporidiosis, a disease cause by the parasite Cryptosporidium, is diarrhea-symptom ailment that affects the small intestine. It is mostly accompanied with dehydration, malabsorption, and death in severe cases. Despite the detrimental effect on the society, nitazoxanide is the only FDA approved drug to treat cryptosporidiosis, but it is only partially effective in children and ineffective in immunodeficient patients. Several works have been done in the quest of ascertaining new drugs for cryptosporidiosis, amongst which is the discovery of triazolopyridazine MMV665917. MMV665917 has an EC50 of 2.1 µM in the cell culture and is orally efficacious in animal C. parvum and C. hominis infection models, but its development has been hindered by its modest inhibition of the hERG ion channel leading to a narrow therapeutic index between anti-Cryptosporidium efficacy and potential for cardiotoxicity. This work focused on the developing structure-activity relationships (SAR) leading to the discovery of SLU-2633. This new lead compound has an Cp EC50 of 0.17 µM leading to a significantly improved projected margin versus the hERG ion channel and oral efficacy in a mouse Cp infection model. SLU-2633 demonstrates a significant advancement towards the identification of a new effective and safe treatment for cryptosporidiosis.

Optimization of MMV665917 to identify new lead compounds for treatment of cryptosporidiosis

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.