Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds
Microtubules continue to be one of the most successful anticancer drug targets and a favorite hit for many naturally occurring molecules. While two of the most successful representative agents in clinical use, the taxanes and the vinca alkaloids, come from terrestrial sources, the sea has also proven to be a rich source of new tubulin-binding molecules. We describe herein the first isolation, structural elucidation and total synthesis of two totally new polyketides isolated from the Madagascan sponge Lithoplocamia lithistoides. Both PM050489 and PM060184 show antimitotic properties in human tumor cells lines at subnanomolar concentrations and display a distinct inhibition mechanism on microtubules. The development of an efficient synthetic procedure has solved the supply problem and, following pharmaceutical development, has allowed PM060184 to start clinical studies as a promising new drug for cancer treatment.
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American Chemical Society
2013
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dig-ica-es-10261-1014692016-02-17T22:27:29Z Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds Martín, María Jesús Coello, Laura Fernández, Rogelio Reyes, Fernando Rodríguez, Alberto Murcia, Carmen Garranzo, María Mateo, Cristina Sánchez-Sancho, Francisco Bueno, Santiago Eguilior, Carlos de Francesch, Andrés Munt, Simón Cuevas, Carmen Microtubules continue to be one of the most successful anticancer drug targets and a favorite hit for many naturally occurring molecules. While two of the most successful representative agents in clinical use, the taxanes and the vinca alkaloids, come from terrestrial sources, the sea has also proven to be a rich source of new tubulin-binding molecules. We describe herein the first isolation, structural elucidation and total synthesis of two totally new polyketides isolated from the Madagascan sponge Lithoplocamia lithistoides. Both PM050489 and PM060184 show antimitotic properties in human tumor cells lines at subnanomolar concentrations and display a distinct inhibition mechanism on microtubules. The development of an efficient synthetic procedure has solved the supply problem and, following pharmaceutical development, has allowed PM060184 to start clinical studies as a promising new drug for cancer treatment. Peer Reviewed 2014-09-01T08:42:38Z 2014-09-01T08:42:38Z 2013 2014-09-01T08:42:38Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.1021/ja404578u issn: 0002-7863 e-issn: 1520-5126 Journal of the American Chemical Society 135: 10164- 10171 (2013) http://hdl.handle.net/10261/101469 10.1021/ja404578u none American Chemical Society |
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Microtubules continue to be one of the most successful anticancer drug targets and a favorite hit for many naturally occurring molecules. While two of the most successful representative agents in clinical use, the taxanes and the vinca alkaloids, come from terrestrial sources, the sea has also proven to be a rich source of new tubulin-binding molecules. We describe herein the first isolation, structural elucidation and total synthesis of two totally new polyketides isolated from the Madagascan sponge Lithoplocamia lithistoides. Both PM050489 and PM060184 show antimitotic properties in human tumor cells lines at subnanomolar concentrations and display a distinct inhibition mechanism on microtubules. The development of an efficient synthetic procedure has solved the supply problem and, following pharmaceutical development, has allowed PM060184 to start clinical studies as a promising new drug for cancer treatment. |
format |
artículo |
author |
Martín, María Jesús Coello, Laura Fernández, Rogelio Reyes, Fernando Rodríguez, Alberto Murcia, Carmen Garranzo, María Mateo, Cristina Sánchez-Sancho, Francisco Bueno, Santiago Eguilior, Carlos de Francesch, Andrés Munt, Simón Cuevas, Carmen |
spellingShingle |
Martín, María Jesús Coello, Laura Fernández, Rogelio Reyes, Fernando Rodríguez, Alberto Murcia, Carmen Garranzo, María Mateo, Cristina Sánchez-Sancho, Francisco Bueno, Santiago Eguilior, Carlos de Francesch, Andrés Munt, Simón Cuevas, Carmen Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds |
author_facet |
Martín, María Jesús Coello, Laura Fernández, Rogelio Reyes, Fernando Rodríguez, Alberto Murcia, Carmen Garranzo, María Mateo, Cristina Sánchez-Sancho, Francisco Bueno, Santiago Eguilior, Carlos de Francesch, Andrés Munt, Simón Cuevas, Carmen |
author_sort |
Martín, María Jesús |
title |
Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds |
title_short |
Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds |
title_full |
Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds |
title_fullStr |
Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds |
title_full_unstemmed |
Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds |
title_sort |
isolation and first total synthesis of pm050489 and pm060184, two new marine anticancer compounds |
publisher |
American Chemical Society |
publishDate |
2013 |
url |
http://hdl.handle.net/10261/101469 |
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