@article{ebe6fa0c80d641b78e815a4804489995,
title = "Targeting the cytochrome bc1 complex of Leishmania parasites for discovery of novel drugs",
abstract = "Endochin-like quinolones (ELQs) are potent and specific inhibitors of cytochrome bc1 from Plasmodium falciparum and Toxoplasma gondii and show promise for novel antiparasitic drug development. To determine whether the mitochondrial electron transport chain of Leishmania parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse ELQs. A cohort of ELQs was selectively toxic to amastigotes of Leishmania mexicana and L. donovani, with 50% inhibitory concentrations (IC50s) in the low micromolar range, but the structurally similar hydroxynaphthoquinone buparvaquone was by far the most potent inhibitor of electron transport, ATP production, and intracellular amastigote growth. Cytochrome bc1 is thus a promising target for novel antileishmanial drugs, and further improvements on the buparvaquone scaffold are warranted for development of enhanced therapeutics.",
author = "Diana Ortiz and Isaac Forquer and Jan Boitz and Radika Soysa and Carolyn Elya and Audrey Fulwiler and Aaron Nilsen and Tamsen Polley and Riscoe, {Michael K.} and Buddy Ullman and Landfear, {Scott M.}",
note = "Funding Information: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128. This support was delivered via the Oregon Clinical and Translational Research Institute of the Oregon Health and Sciences University. This work was also supported by R21 AI102874 (to S.M.L.), R21 AI023682 (to B.U.), and R21 AI100569 (to M.K.R.). This project was additionally supported by funds from the Veterans Affairs Merit Review Program, award number i01 BX003312 (to M.K.R.), and by funds from the U.S. Department of Defense Peer Reviewed Medical Research Program (PR130649) (to M.K.R.). This work, including the efforts of Michael K. Riscoe, was funded by Department of Veterans Affairs (i01 BX003312). This work, including the efforts of Michael K. Riscoe, was funded by Department of Defense (PR130649). This work, including the efforts of Michael K. Riscoe, Buddy Ullman, and Scott M. Landfear, was funded by HHS | National Institutes of Health (NIH) (UL1TR000128, AI102874, and AI023682). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding institutions. Publisher Copyright: Copyright {\textcopyright} 2016, American Society for Microbiology. All Rights Reserved.",
year = "2016",
month = aug,
doi = "10.1128/AAC.00850-16",
language = "English (US)",
volume = "60",
pages = "4972--4982",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "8",
}