Session Speaker
Potent Anti-inflammatory Activity of Novel Microtubule-Modulating Brominated Noscapine Analogs
Susu Zughaier, Prasanthi Karna, David Stephens, Ritu Aneja
USA


Acute and chronic inflammation underlies many disease states including atherosclerosis, arthritis, bowel disease and even cancer. Although controlled levels of inflammation are essential for human host defense and for maintaining homeostatic balance, chronic and exaggerated inflammation is adversial to the host. Thus, there is an ongoing search for effective anti-inflammatory drugs that are not toxic yet control exaggerated or chronic inflammation. 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 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. In conclusion, we identified brominated noscapines as anti-inflammatory molecules that exert anti-inflammatory activity by impeding TLR-induced signaling via sluggish microtubule dynamics and by inducing autophagy.