Document Type

Thesis

Date of Degree Completion

Fall 2023

Degree Name

Master of Science (MS)

Department

Biology

Committee Chair

Blaise Dondji

Second Committee Member

Timothy Beng

Third Committee Member

Gabrielle Stryker

Abstract

The leishmaniases are a group of vector-borne parasitic diseases that affect many developing countries including parts of Africa, India, and the Middle East in addition to Southern Europe and the Americas. It is estimated that worldwide, there are about 3 million new cases of leishmaniases each year leading to as many as 50,000 fatalities annually. The parasites that cause leishmaniasis belong to the genus Leishmania spp and are transmitted by the female phlebotomine sand fly. There are three clinical forms of the infection: visceral, mucocutaneous, and cutaneous. However, the focus of this paper is on cutaneous leishmaniasis that causes skin lesions and ulcers. Current drugs used to treat leishmaniasis such as the state-of-the-art medicine, amphotericin B, are highly toxic with potentially life-threatening side effects. Importantly, drug resistance to leishmaniasis continues to pose a challenge to the medicinal community. It is therefore urgent to identify new therapeutics with reduced toxicity. To contribute to this goal, synthetized 4-thiazolidinone compounds were screened for activity against Leishmania spp. A colorimetric assay with Alamar Blue reagent was utilized to assess the viability of the parasites. The compounds were also screened for toxicity to mammalian cells using BrdU kits to mark de novo DNA synthesis in proliferating cells. Ultimately, out of 39 thiazolidinones that were tested, 16 were found to be effective at killing the Leishmania at the same level, or better than our control, amphotericin B. Selected compounds tested in a dose-response assay showed activity at concentration as low as 25 μg/mL, a level of activity similar to that of Amphotericin B. Structure-activity analysis shows that the addition of certain substituents such as a sulfone group to a compound that was biologically inactive renders it active. Together, our data demonstrate that functionalized thiazolidinones have in vivo anti-Leishmania activity that is directly linked to their chemical structures.

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