Antileishmanial Activity of Compounds Derived from the Medicines for Malaria Venture Open Access Box against Intracellular Leishmania major Amastigotes |
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| Authors: | Mozna Khraiwesh Susan Leed Norma Roncal Jacob Johnson Richard Sciotti Philip Smith Lisa Read Robert Paris Thomas Hudson Mark Hickman Max Grogl |
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| Affiliation: | Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, Washington; Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland |
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| Abstract: | Leishmaniasis is a complex tropical disease caused by kinetoplastid parasitic protozoa of the genus Leishmania and is transmitted by the sand fly insect vector. Cutaneous leishmaniasis (CL) is the most common form of this disease, and CL infections often result in serious skin lesions and scars. CL remains a public health problem in many endemic countries worldwide because of the absence of effective, safe, and cost-effective drugs for treatment. One of the strategies we chose to use to find novel chemical entities worthy of further development as antileishmanials involved screening synthetic and natural products libraries. In our study, we developed a Leishmania major intracellular amastigote assay that uses the activity of luciferase as a measure of parasite proliferation and used this assay to screen a collection of 400 compounds obtained from Medicines for Malaria Venture (MMV) for their antileishmanial activity. Our results showed that 14 compounds identified by MMV as antimalarial drugs have antileishmanial activity and can potentially be optimized for CL drug development. |
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