Designing anti-inflammatory drugs from parasitic worms: a synthetic small molecule analogue of the Acanthocheilonema viteae product ES-62 prevents development of collagen-induced arthritis: Helminth-based synthetic compound protects against CIA

Lamyaa Al-Riyami, Miguel Pineda, Justyna Rzepecka, Judith Huggan, Abedawn Khalaf, Colin Suckling, David Rodgers, Margaret Harnett, William Harnett, Fraser Scott

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62 Citations (Scopus)

Abstract

In spite of increasing evidence that parasitic worms may protect humans from developing allergic and autoimmune diseases, and the continuing identification of defined helminth-derived immunomodulatory molecules, to date no new anti-inflammatory drugs have been developed from these organisms. We have approached this matter in a novel manner by synthesizing a library of drug-like small molecules based upon phosphorylcholine, the active moiety of the anti-inflammatory Acanthocheilonema viteae product, ES-62, which as an immunogenic protein is unsuitable for use as a drug. Following preliminary in vitro screening for inhibitory effects on relevant macrophage cytokine responses, a sulfone-containing phosphorylcholine analogue (11a) was selected for testing in an in vivo model of inflammation, collagen-induced arthritis (CIA). Testing revealed that (11a) was as effective as ES-62 in protecting DBA/1 mice from developing CIA and mirrored its mechanism of action in downregulating the TLR/IL1R transducer, MyD88. (11a) is thus a novel prototype for anti-inflammatory drug development.
Original languageEnglish
Pages (from-to)9982-10002
Number of pages20
JournalJournal of Medicinal Chemistry
Volume56
DOIs
Publication statusPublished - 2013

Keywords

  • arthritis
  • helminth
  • drug development
  • immunomodulation

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