Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.
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.
Zughaier
Susu
S
Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America. szughai@emory.edu
Karna
Prasanthi
P
Stephens
David
D
Aneja
Ritu
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000996:Antitussive Agents / Q000737:chemistry / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054879:Halogenation; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D008954:Models, Biological; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D009665:Noscapine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000996:Antitussive Agents; D054357:Chemokine CXCL10; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4; D050257:Tubulin Modulators; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D009665:Noscapine