Onchocerca volvulus Molting Inhibitors Identified through Scaffold Hopping.
The anthelmintic closantel has shown promise in abrogating the L3 molting of Onchocerca volvulus, the causative agent of the infectious disease onchocerciasis. In our search for alternative scaffolds, we utilized a fragment replacement/modification approach to generate novel chemotypes with improved chitinase inhibitory properties. Further evaluation of the compounds unveiled the potential of urea-tropolones as potent inhibitors of O. volvulus L3 molting.
Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute of Research and Medicine, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Major
M
Gooyit
Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute of Research and Medicine, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Tyler L
TL
Harris
Lindsley F. Kimball Research Institute, New York Blood Center , New York, New York 10065, United States.
Nancy
N
Tricoche
Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute of Research and Medicine, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Sacha
S
Javor
Lindsley F. Kimball Research Institute, New York Blood Center , New York, New York 10065, United States.
Sara
S
Lustigman
Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute of Research and Medicine, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Kim D
KD
Janda
molting; onchocerciasis; tropolones