1. Academic Validation
  2. Antitumor actinopyranones produced by Streptomyces albus POR-04-15-053 isolated from a marine sediment

Antitumor actinopyranones produced by Streptomyces albus POR-04-15-053 isolated from a marine sediment

  • J Nat Prod. 2011 Jul 22;74(7):1590-6. doi: 10.1021/np200196j.
Carmen Schleissner 1 Marta Pérez Alejandro Losada Pilar Rodríguez Cristina Crespo Paz Zúñiga Rogelio Fernández Fernando Reyes Fernando de la Calle
Affiliations

Affiliation

  • 1 Drug Discovery Area, PharmaMar SAU , Avenida de los Reyes 1, 28770-Colmenar Viejo, Madrid, Spain.
Abstract

Four new antitumor pyranones, PM050511 (1), PM050463 (2), PM060054 (3), and PM060431 (4), were isolated from the cell extract of the marine-derived Streptomyces albus POR-04-15-053. Their structures were elucidated by a combination of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS. They consist of an α-methoxy-γ-pyrone ring containing a highly substituted tetraene side chain glycosylated at C-10 in the case of 1 and 4. Compounds 1 and 4 displayed strong cytotoxicity against three human tumor cell lines with GI₅₀ values in the submicromolar range, whereas 2 showed subnanomolar activity as an inhibitor of EGFR-MAPK-AP1-mediated mitogenic signaling, causing inhibition of EGF-mediated AP1 trans-activation and EGF-mediated ERK activation and slight inhibition of EGF-mediated JNK activation. Taken together, these results suggest that members of the pyranone family of compounds could be developed as potential antitumor agents.

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