Chemistry Seminar with Dr. Marvin Meyers from Saint Louis University at 4:00pm

Abstract: Cryptosporidiosis is a neglected diarrheal disease that is caused by infection of the intestines by the parasite Cryptosporidium. This disease disproportionately afflicts young and malnourished children in low-middle income countries resulting 132,000 deaths annually, greatly exceeding that of all other recognized neglected tropical diseases. The only FDA-approved therapeutic for cryptosporidiosis, nitazoxanide, is only marginally effective in malnourished children and is ineffective in immunocompromised adults. To address this significant unmet medical need, we have conducted screening of known anti- Plasmodium compounds and other advanced clinical compound libraries for leads for the development of novel anti-Cryptosporidium therapeutics. Three series of compounds, each with a unique mode of action, have been advanced to medicinal chemistry optimization. The most potent compounds identified to date have EC50 values ranging from 10-200 nM in HCT-8 cells infected with C. parvum. Compounds from each class have oral in vivo efficacy in an immunocompromised mouse model of Cryptosporidium infection. Ongoing efforts to identify a safe and potent therapeutic for preclinical development will be discussed