Introduction: 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 occurrence
of leishmaniasis continues to be more prevalent. Sulfonamides are a class of compounds with
medicinal properties which have been used to treat bacterial and parasitic disease via various pathways
especially as antimetabolites for folic acid.
Methods: New derivatives 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 brain heart infusion (BHI) medium and treated with
varying concentrations of the new sulfonamide compounds. Light microscopy and viability tests were
used to assess the cells with and without treatment.
Discussion: A non-water soluble sulfonamide was determined to have 90-96% viability inhibition 24
hours after treatment with 100 μM final concentration. Because Leishmania are also autotrophs for folate
precursors, the folic acid pathway was identified as a target for sulfonamide inhibition. When folic
acid was added to untreated Leishmania, cell proliferation increased. A water soluble derivative of the
inhibitory sulfonamide was synthesized and evaluated, resulting in less viability inhibition with a single
dose (approximately 70% viability inhibition after 24 hours with 100 μM final concentration), but additive
inhibition with multiple doses of the compound.
Results: However, the potential mechanism of inhibition was different between the water-soluble and
non-water soluble sulfonamides. The inhibitory effects and potential pathways of inhibition indicate that
these compounds may be new treatments for this disease.