Potent Anti-Inflammatory Activity of Novel Microtubule-Modulating Brominated Noscapine Analogs

• Type of Material: Article
• Authors: Susu M Zughaier, Emory University; Prasanthi Karna, Georgia State University; David S Stephens, Emory University; Ritu Aneja, Georgia State University
• Language: English
• Date: 2010
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2010 Zughaier et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009165
• Title of Journal or Parent Work: PLoS Biology
• ISSN: 1544-9173
• Volume: 5
• Issue: 2
• Start Page: e9165
• End Page: e9165
• Grant/Funding Information: This work was supported by grants to RA from the Department of Defense (PC073104), and National Cancer Institute (K99 CA131489); and to DS from NIH (R01 AI033517). SZ, DS and RA acknowledge financial support from Georgia Research Alliance
• Keywords: chemokines; inflammation; nitric oxide; cytokines; macrophages; toxicity
• Research Categories: Health Sciences, Immunology; Health Sciences, Toxicology

Abstract

Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules.