Macrophilones from the Marine Hydroid Macrorhynchia philippina Can Inhibit ERK Cascade Signaling

作者：Yan, Pengcheng; Ritt, Daniel A.; Zlotkowski, Katherine; Bokesch, Heidi R.; Reinhold, William C.; Schneekloth, John S., Jr.; Morrison, Deborah K.^*; Gustafson, Kirk R.^*

来源：Journal of Natural Products, 2018, 81(7): 1666-1672.

DOI：10.1021/acs.jnatprod.8b00343

• GARVEIA-ANNULATA
• EUDENDRIUM-GLOMERATUM
• STRUCTURE ELUCIDATION
• TRIDENTATA-MARGINATA
• NATURAL-PRODUCTS
• A-C
• METABOLITES
• SUMOYLATION
• STEROLS
• SPONGE

Six new macrophilone-type pyrroloiminoquines were isolated and identified from an extract of the marine hydroid Macrorhynchia philippina. The proton deficient and heteroatom-rich structures of macrophilones B-G (2-7) were elucidated by spectroscopic analysis and comparison of their data with those of the previously reported metabolite macrophilone A (1). Compounds 1-7 are the first pyrroloiminoquines to be reported from a hydroid. The macrophilones were shown to inhibit the enzymatic conjugation of SUMO to peptide substrates, and macrophilones A (1) and C (3) exhibit potent and selective cytotoxic properties in the NCI-60 anticancer screen. Bioinformatic analysis revealed a close association of the cytotoxicity profiles of 1 and 3 with two known B-Raf kinase inhibitory drugs. While compounds 1 and 3 showed no kinase inhibitory activity, they resulted in a dramatic decrease in cellular protein levels of selected components of the ERK signal cascade. As such, the chemical scaffold of the macrophilones could provide small-molecule therapeutic leads that target the ERK signal transduction pathway.

• 出版日期2018-7
• 单位温州医科大学