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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 ?-carboline alkaloid scaffolding as a chitinase inhibitor that is capable of penetrating the worm cuticle. Herein, we disclose the rich polypharmacology of the ?-carboline class of compounds as an approach to abrogate the molting of the parasite and thus the initiation of infection in the human host.

SUBMITTER: Gooyit M

PROVIDER: S-EPMC4360149 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Exploiting the Polypharmacology of ß-Carbolines to Disrupt O. volvulus Molting.

Gooyit Major M Tricoche Nancy N Javor Sacha S Lustigman Sara S Janda Kim D KD

ACS medicinal chemistry letters 20150120 3

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 al ...[more]

PMID: 25815157

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