Canales Mayordomo, María ÁngelesBargsten, KatjaBennani, Youssef L.Díaz, Fernando J.Jiménez Barbero, JesúsOliva, María A.Prota, Andrea E.Rodríguez Salarichs, J.Steinmetz, Michel O.2026-01-132026-01-132020-08-13Oliva M A, Prota A E, Rodríguez-Salarichs J, Bennani Y L, Jiménez-Barbero J, Bargsten K, Canales A, Steinmetz M O, Fernando Díaz J, Structural Basis of Noscapine Activation for Tubulin Binding. J. Med. Chem. 2020, 63, 15, 8495–850110.1021/acs.jmedchem.0c00855https://hdl.handle.net/20.500.14352/129977Noscapine is a natural alkaloid that is used as an antitussive medicine. However, it also acts as a weak anticancer agent in certain in vivo models through a mechanism that is largely unknown. Here, we performed structural studies and show that the cytotoxic agent 7A-O-demethoxy-amino-noscapine (7A-aminonoscapine) binds to the colchicine site of tubulin. We suggest that the 7A-methoxy group of noscapine prevents binding to tubulin due to a steric clash of the compound with the T5-loop of α-tubulin. We further propose that the anticancer activity of noscapine arises from a bioactive metabolite that binds to the colchicine site of tubulin to induce mitotic arrest through a microtubule cytoskeleton-based mechanism.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00855https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00855restricted access547Matrix CORCEMA analysisComplete relaxationColchicineMechanismCiencias23 Química