Antileishmanial Activity of Compounds Derived from the MMV Open Access Box Against Intracellular Leishmania major Amastigotes

03 Feb 2016

Mozna Khraiwesh, Susan Leed, Norma Roncal, Jacob Johnson, Richard Sciotti, Philip Smith, Lisa Read, Robert Paris, Thomas Hudson, Mark Hickman and Max Grogl.

The American Journal of Tropical Medicine and Hygiene

DOI: 10.4269/ajtmh.15-0448.

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.

Disclaimer: Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

Read the full article on the American Journal of Tropical Medicine and Hygiene site.