Brominated Noscapine

About

Introduction: The innate immune system plays a crucial role in host defense and homeostasis. Innate immune responses are induced when pattern recognition receptors such as Toll-like receptors (TLR) sense the presence of pathogen associated molecules or endogenous ‘‘danger’’ molecules released by damaged cells. Although acute innate pathway inflammatory responses promote termination of infection and wound healing, chronic activation of this pathway can lead to tissue damage and fibrosis and contribute to various disease states such as atherosclerosis, arthritis, and inflammatory bowel disease. There is a need for new non-toxic agents that can treat inflammation. Technology: Noscapinoids constitute an emerging class of small-molecule microtubule-modulating agents that do not alter the total polymer mass of tubulin. Noscapinoids, such as the brominated analogs of Noscapine, have been shown to have significant anticancer activity and are non-toxic at doses as high as 300 mg/kg. Perhaps due to limited effects on microtubule dynamics, noscapinoids do not perturb the transport functions of microtubules in a variety of cell types such as post-mitotic neurons and have no apparent histo-, hemato-, immuno- or neuronal toxicity. Another unique property of noscapinoids is their oral bioavailability. Based upon structural similarity with well known the anti-inflammatory colchicine, Georgia State University and Emory University researchers investigated the innate immune pathway anti-inflammatory activity of noscapine and its brominated analogs in vitro. The researchers discovered the anti-inflammatory activity of brominated noscapine analogs inin vitromodels mimicking septic and sterile innate immune pathway induced inflammation. The research team demonstrated that these drugs inhibit TNFa, IL-8 and nitric oxide release upon challenge with various TLR and non-TLR ligands. Furthermore, brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability.