Al-Riyami, Lamyaa, Pineda, Miguel A., Rzepecka, Justyna, Huggan, Judith K., Khalaf, Abedawn I., Suckling, Colin J., Scott, Fraser J., Rodgers, David T., Harnett, Margaret M. and Harnett, William (2013) Designing Anti-inflammatory Drugs from Parasitic Worms: A Synthetic Small Molecule Analogue of theAcanthocheilonema viteaeProduct ES-62 Prevents Development of Collagen-Induced Arthritis. Journal of Medicinal Chemistry, 56 (24). pp. 9982-10002. ISSN 0022-2623

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/IL-1R transducer, MyD88. 11a is thus a novel prototype for anti-inflammatory drug development

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