Brain‐Penetrant Triazolopyrimidine and Phenylpyrimidine Microtubule Stabilizers as Potential Leads to Treat Human African Trypanosomiasis |
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| Authors: | Dr. Ludovica Monti Steven C Wang Dr. Killian Oukoloff Dr. Amos B. Smith III Dr. Kurt R. Brunden Dr. Conor R. Caffrey Dr. Carlo Ballatore |
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| Affiliation: | 1. Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La?Jolla, CA, USA;2. Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA;3. Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA |
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| Abstract: | In vitro whole‐organism screens of Trypanosoma brucei with representative examples of brain‐penetrant microtubule (MT)‐stabilizing agents identified lethal triazolopyrimidines and phenylpyrimidines with sub‐micromolar potency. In mammalian cells, these antiproliferative compounds disrupt MT integrity and decrease total tubulin levels. Their parasiticidal potency, combined with their generally favorable pharmacokinetic properties, which include oral bioavailability and brain penetration, suggest that these compounds are potential leads against human African trypanosomiasis. |
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| Keywords: | human African trypanosomiasis microtubules phenylpyrimidines triazolopyrimidines Trypanosoma brucei |
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