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

Al-Riyami, Lamyaa and Pineda, Miguel and Rzepecka, Justyna and Huggan, Judith and Khalaf, Abedawn and Suckling, Colin and Rodgers, David and Harnett, Margaret and Harnett, William and Scott, Fraser (2013) 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. Journal of Medicinal Chemistry, 56. pp. 9982-10002. ISSN 0022-2623

Full text not available in this repository.Request a copy from the Strathclyde author

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.