2020 Annual Meeting Poster: Hannah Corman

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2020 Annual Meeting Poster: Hannah Corman

2020 Annual Meeting Poster: Hannah Corman

Presentation Title: Investigation of a Series of 1,4-diaryl-pyrazolo-pyridinones as Anti-Leishmanial Agents

Author Name(s): Hannah N. Corman1, Douglas A. Shoue1, Bruce J. Melancon2, and Mary Ann McDowell1

Author Department and School Affiliation: 1Eck Institute for Global Health, University of Notre Dame; 2Vanderbilt Center for Neuroscience and Drug Discovery, Vanderbilt University

Abstract: Leishmaniasis is a grouping of diseases caused by the protozoan parasites Leishmania spp., affecting 12 million people per year with almost 310 million people at risk. Leishmaniasis has a range of clinical manifestations, from self-healing skin lesions to fatality. Chemotherapies like intravenous pentavalent antimonials are highly toxic, while oral treatment options such as paromomycin and miltefosine have been used more as incidences of disease relapse and drug resistance develop, emphasizing the importance of identifying new and effective chemotherapies. We developed a novel, target—free fluorometric high-throughput screen (HTS) to identify small molecules with anti-leishmanial activity. Screening of 10,000 small molecules from the ChemBridge DIVERset-EXPTM library yielded 210 compounds that killed 80 percent of parasites, resulting in a hit rate of 2.1 percent. One hundred nine (109) molecular scaffolds were represented within the hit compounds; one scaffold that exhibits potent anti-leishmanial activity was 1,4-diaryl-pyrazolo-pyridinone (1,4-DAPP). A total of 27 novel 1,4-DAPP compounds were synthesized and anti-leishmanial efficacy and host cell toxicity was determined using L. donovani mCherry expressing amastigotes and THP-1 macrophages; successful drug treatment was considered when the IC50 value was less than 10μM and the CC50 value was greater than 50μM. Future studies include in vitro and in vivo characterization of these novel compounds.

|2020-09-08T12:18:52-04:00September 2nd, 2020|Annual Meeting Posters|0 Comments

About the Author: Jessica Hall

Jessica Hall

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