Isolation and First Total Synthesis of PM050489 and PM060184, Two New Marine Anticancer Compounds

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• 作者：Mar铆a Jes煤s Mart铆n ; Laura Coello ; Rogelio Fern谩ndez ; Fernando Reyes ; Alberto Rodr铆guez ; Carmen Murcia ; Mar铆a Garranzo ; Cristina Mateo ; Francisco S谩nchez-Sancho ; Santiago Bueno ; Carlos de Eguilior ; Andr茅s Francesch ; Simon Munt ; Carmen Cuevas
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：July 10, 2013
• 年：2013
• 卷：135
• 期：27
• 页码：10164-10171
• 全文大小：424K
• 年卷期：v.135,no.27(July 10, 2013)
• ISSN：1520-5126

文摘

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.