Al-Riyami, L., Pineda, M.A. , Rzepecka, J., Huggan, J.K., Khalaf, A.I., Suckling, C.J., Scott, F.J., Rodgers, D.T., Harnett, M.M. and Harnett, W. (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. Journal of Medicinal Chemistry, 56(24), pp. 9982-10002. (doi: 10.1021/jm401251p)
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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/IL-1R transducer, MyD88. 11a is thus a novel prototype for anti-inflammatory drug development.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Harnett, Professor Margaret and Pineda, Dr Miguel |
Authors: | Al-Riyami, L., Pineda, M.A., Rzepecka, J., Huggan, J.K., Khalaf, A.I., Suckling, C.J., Scott, F.J., Rodgers, D.T., Harnett, M.M., and Harnett, W. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of Medicinal Chemistry |
ISSN: | 0022-2623 |
ISSN (Online): | 1520-4804 |
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