title: Antitumor actinopyranones produced by Streptomyces albus POR-04-15-053 isolated from a marine sediment.
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.
authors: Drug Discovery Area, PharmaMar SAU , Avenida de los Reyes 1, 28770-Colmenar Viejo, Madrid, Spain.
authors: Carmen
authors: C
authors: Schleissner
authors: Marta
authors: M
authors: Pérez
authors: Alejandro
authors: A
authors: Losada
authors: Pilar
authors: P
authors: Rodríguez
authors: Cristina
authors: C
authors: Crespo
authors: Paz
authors: P
authors: Zúñiga
authors: Rogelio
authors: R
authors: Fernández
authors: Fernando
authors: F
authors: Reyes
authors: Fernando
authors: F
authors: de la Calle
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000187:drug effects; D005260:Female; D019015:Geologic Sediments / Q000382:microbiology; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008386:Marine Biology; D015394:Molecular Structure; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011753:Pyrones; D018808:Transcription Factor AP-1; D066246:ErbB Receptors; D048670:MAP Kinase Kinase 4