title: Exploiting the Polypharmacology of ß-Carbolines to Disrupt O. volvulus Molting.
abstract: Onchocerciasis is an infection caused by the filarial worm Onchocerca volvulus, which can eventually result in blindness. The lack of an effective macrofilaricide and the possible development of ivermectin-resistant strains of O. volvulus necessitate the need for alternative treatment strategies. We have shown that targeting the L3-stage-specific chitinase OvCHT1 impairs the shedding of the filarial cuticle. In our continued efforts to discover OvCHT1 inhibitors, we identified the β-carboline alkaloid scaffolding as a chitinase inhibitor that is capable of penetrating the worm cuticle. Herein, we disclose the rich polypharmacology of the β-carboline class of compounds as an approach to abrogate the molting of the parasite and thus the initiation of infection in the human host.
authors: 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.
authors: Major
authors: M
authors: Gooyit
authors: Lindsley F. Kimball Research Institute, New York Blood Center , New York, New York 10065, United States.
authors: Nancy
authors: N
authors: Tricoche
authors: 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.
authors: Sacha
authors: S
authors: Javor
authors: Lindsley F. Kimball Research Institute, New York Blood Center , New York, New York 10065, United States.
authors: Sara
authors: S
authors: Lustigman
authors: 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.
authors: Kim D
authors: KD
authors: Janda
keywords: Onchocerciasis; chitinase inhibitor; polypharmacology; β-carbolines