Macrophilones from the marine hydroid Macrorhynchia philippina can inhibit ERK cascade signaling
Yan, P.; Ritt, D.A.; Zlotkowski, K.; Bokesch, H.R.; Reinhold, W.C.; Schneekloth, J.S.; Morrison, D.K.; Gustafson, K.R. (2018). Macrophilones from the marine hydroid Macrorhynchia philippina can inhibit ERK cascade signaling. J. Nat. Prod. 81(7): 1666-1672. https://dx.doi.org/10.1021/acs.jnatprod.8b00343
In: Journal of Natural Products. American Chemical Society/American Society of Pharmacognosy: Washington DC. ISSN 0163-3864; e-ISSN 1520-6025, more
|  |
| Authors | | Top |
- Yan, P.
- Ritt, D.A.
- Zlotkowski, K.
- Bokesch, H.R.
|
- Reinhold, W.C.
- Schneekloth, J.S.
- Morrison, D.K.
- Gustafson, K.R.
|
|
| Abstract |
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. |
|
