Pest Management ScienceVolume 61, Issue 11 , Pages 1069 - 1076Evaluation of phenylaminopyrimidines as antifungal protein kinase inhibitors |
| Christian Pillonel * |
| Syngenta Crop Protection AG, CH-4002 Basel, Switzerland |
| email: Christian Pillonel (chrispill@bluewin.ch) |
*Correspondence to Christian Pillonel, Hauptstrasse 67A, 4312 Magden, Switzerland
| Keywords |
| fungicide • phenylaminopyrimidine • Neurospora crassa • cyclin-dependent protein kinase • mitogen-activated protein kinase • cell cycle • osmoregulation |
| Abstract |
| The effects of diverse phenylaminopyrimidines (PAP), namely PAP-pyridines (type A), PAP-pyrazoles (type B) and PAP-thiazoles (type C), on Neurospora crassa Shear & Dodge has been investigated. The results revealed that type A strongly inhibit the in vitro growth of N crassa, whereas types B and C are much less active. A significant correlation was observed between the Neurospora growth inhibition and the intrinsic activity of type A compounds on the cyclin-dependent protein kinase p34CDC2 of starfish, suggesting that the target of phenylaminopyrimidines in fungi is a cyclin-dependent protein kinase (CDK). The phenylaminopyrimidine-binding CDKs Phoss (major band) and CDC2 (minor band) involved in phosphorus uptake, glycogen synthesis and the cell cycle were identified from N crassa by affinity chromatography on phenylaminopyrimidine-sepharose. Comparative experiments with different protein kinases revealed the importance of the side chain of phenylaminopyrimidines for their target selectivity. A type B compound was found to selectively inhibit the MAP-kinase OS-2 involved in the osmoregulatory pathway of Neurospora. Copyright © 2005 Society of Chemical Industry |