Bleaching activities of substituted pyrimidines and structure-activity comparison to related heterocyclic derivatives

The bleaching mode of action of 2,4-diphenyl pyrimidine derivatives was est ablished by determination of the decreased formation of colored carotenoids and the accumulation of phytoene. Direct inhibition of the target enzyme p hytoene desaturase was demonstrated by in vitro assays, which excludes p-hy droxyphenylpyruvate dioxygenase as a mode of action target. Furthermore, tr ansgenic tobacco plants which express a bacterial phytoene desaturase that lacks the inhibition site also exhibited resitance to the pyrimidines. Stru cture-activity investigations of direct interaction of the pyrimidine deriv atives with the target enzyme were carried out and established the importan ce of a defined length of the 5-substituent. Comparison of different centra l heterocycles with similar substitutions revealed that the inhibitory acti vities of pyrimidines and pyrimidinones were higher than the activities of pyridines and triazines. It is proposed that the important features for int eraction/inhibition of phytoene desaturase are the negative charge at N-3 a nd the space filing of the 5-substituents. (C) 2001 Academic Press.