RT Journal Article
T1 Structural basis of noscapine activation for tubulin binding
A1 Canales Mayordomo, María Ángeles
A1 Bargsten, Katja
A1 Bennani, Youssef L.
A1 Díaz, Fernando J.
A1 Jiménez Barbero, Jesús
A1 Oliva, María A.
A1 Prota, Andrea E.
A1 Rodríguez Salarichs, J.
A1 Steinmetz, Michel O.
AB Noscapine 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.
PB ACS publications
YR 2020
FD 2020-08-13
LK https://hdl.handle.net/20.500.14352/129977
UL https://hdl.handle.net/20.500.14352/129977
LA eng
NO Oliva 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, 8495–8501
NO Agencia española de investigación
NO Instituto de la Salud Carlos III
NO Swiss National Science Foundation (SNSF)
DS Docta Complutense
RD 19 ene 2026