Issue 1, 2013

Truncated militarinone fragments identified by total chemical synthesis induce neurite outgrowth

Abstract

A group of natural products produced by entomopathogenic fungi has recently been shown to induce neurite outgrowth in the absence of nerve growth factor (NGF) in pheochromocytoma PC-12 cell culture. After completion of a total synthesis program, we continued our efforts in reducing complexity by synthetically preparing truncated analogs. Using this approach we were able to not only significantly simplify the structures but also decrease the minimum concentration needed for neuritogenic activity by a factor of 20. This activity was suppressed in the presence of an ERK1/2 inhibitor suggesting activation of the mitogen activated protein kinase (MAPK) pathway as a potential mode of action of these pyridone alkaloids.

Graphical abstract: Truncated militarinone fragments identified by total chemical synthesis induce neurite outgrowth

Supplementary files

Article information

Article type
Concise Article
Submitted
03 Jul 2012
Accepted
10 Aug 2012
First published
13 Aug 2012

Med. Chem. Commun., 2013,4, 135-139

Truncated militarinone fragments identified by total chemical synthesis induce neurite outgrowth

F. Schmid, H. J. Jessen, P. Burch and K. Gademann, Med. Chem. Commun., 2013, 4, 135 DOI: 10.1039/C2MD20181J

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