Inhibitory Effects of Unique Sulfonamides on Leishmania tarentolae and Potential Pathway of Inhibition

Leishmaniasis is an endemic disease caused by the protozoan parasite Leishmania. Current treatments for the parasite are limited by cost, availability, and drug resistance as the worldwide occurrence of leishmaniasis continues to be more prevalent. Sulfonamides are a class of compounds with medicinal properties that have been used to treat bacterial and parasitic diseases via various pathways. In this study, newly synthesized, unique structural analogs of sulfonamide compounds were assessed for their impact on Leishmania cell viability and potential pathways for inhibition were evaluated. Leishmania tarentolae (ATCC Strain 30143) axenic promastigote cells were grown in BHI medium and treated with varying concentrations of the unique sulfonamide compounds. Light microscopy and viability tests were used to assess the cells with and without treatment. Recombinant Leishmania major dihydrofolate reductase-thymidylate synthase (DHFR-TS) bifunctional enzyme was expressed in E. coli, extracted, and purified. DNA sequencing at UIUC confirmed the gene was expressed correctly, but the recombinant protein did not exhibit catalytic activity. Future work should include evaluation of the inhibitory effects of the sulfonamides on the recombinant DHFR-TS. The conclusions of this work will help determine potential applications for tested sulfonamides improving future medicinal therapies for this disease