Discovery and Optimization of Tambjamines As a Novel Class of Antileishmanial Agents.
Published In
Journal of Medicinal Chemistry
Document Type
Citation
Publication Date
5-9-2024
Abstract
Leishmaniasis is a neglected tropical disease that is estimated to afflict over 12 million people. Current drugs for leishmaniasis suffer from serious deficiencies, including toxicity, high cost, modest efficacy, primarily parenteral delivery, and emergence of widespread resistance. We have discovered and developed a natural product-inspired tambjamine chemotype, known to be effective against spp, as a novel class of antileishmanial agents. Herein, we report in vitro and in vivo antileishmanial activities, detailed structure-activity relationships, and metabolic/pharmacokinetic profiles of a large library of tambjamines. A number of tambjamines exhibited excellent potency against both and parasites with good safety and metabolic profiles. Notably, tambjamine offered excellent potency and provided partial protection to leishmania-infected mice at 40 and/or 60 mg/kg/10 days of oral treatment. This study presents the first account of antileishmanial activity in the tambjamine family and paves the way for the generation of new oral antileishmanial drugs.
Rights
© 2024 American Chemical Society
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DOI
10.1021/acs.jmedchem.4c00517
Persistent Identifier
https://archives.pdx.edu/ds/psu/41822
Citation Details
Kancharla, P., Ortiz, D., Fargo, C. M., Zhang, X., Li, Y., Sanchez, M., Kumar, A., Yeluguri, M., Dodean, R. A., Caridha, D., Madejczyk, M. S., Martin, M., Jin, X., Blount, C., Chetree, R., Pannone, K., Dinh, H. T., DeLuca, J., Evans, M., … Landfear, S. M. (2024). Discovery and Optimization of Tambjamines as a Novel Class of Antileishmanial Agents. Journal of Medicinal Chemistry.