Sulfonamides as Inhibitors of Leishmania – Potential New Treatments for Leishmaniasis

Title:Sulfonamides as Inhibitors of Leishmania – Potential New Treatments for Leishmaniasis

Volume: 15 Issue: 1

Author(s): Jade Katinas*, Rachel Epplin, Christopher Hamaker and Marjorie A. Jones

Affiliation:

• Department of Chemistry, Illinois State University, Campus Box 4160, Normal, IL,United States

Keywords: Leishmaniasis, Leishmania, sulfonamide, cellular inhibition, folic acid pathway, promastigote.

Abstract: 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.

Cite this article as:

Katinas Jade*, Epplin Rachel, Hamaker Christopher and Jones A. Marjorie, Sulfonamides as Inhibitors of Leishmania – Potential New Treatments for Leishmaniasis, Anti-Infective Agents 2017; 15 (1) . https://dx.doi.org/10.2174/2211352515666170216143401

DOI https://dx.doi.org/10.2174/2211352515666170216143401	Print ISSN 2211-3525
Publisher Name Bentham Science Publisher	Online ISSN 2211-3533